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Abstract

There is growing concern that metal contamination functions as a selective agent in the proliferation of antibiotic resistance. Documented associations between the types and levels of metal contamination and specific patterns of antibiotic resistance suggest that several mechanisms underlie this co-selection process. These co-selection mechanisms include co-resistance (different resistance determinants present on the same genetic element) and cross-resistance (the same genetic determinant responsible for resistance to antibiotics and metals). Indirect but shared regulatory responses to metal and antibiotic exposure such as biofilm induction also represent potential co-selection mechanisms used by prokaryotes. Metal contamination, therefore, represents a long-standing, widespread and recalcitrant selection pressure with both environmental and clinical importance that potentially contributes to the maintenance and spread of antibiotic resistance factors.

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... Environmental contamination influences antibiotic resistance (AR) and the emergence of AR in bacteria has remained a public health concern. The existence of antibiotic resistant bacteria (ARB) and the AR behaviour have been observed in both clinical and non-clinical samples (Baker--Austin et al., 2006;Goryluk-Salmonowicz and Popowska, 2019;Seiler and Berendonk, 2012). The AR is conferred on bacteria by genes existing in the chromosomes and the MGEs (Baker-Austin et al., 2006). ...
... The existence of antibiotic resistant bacteria (ARB) and the AR behaviour have been observed in both clinical and non-clinical samples (Baker--Austin et al., 2006;Goryluk-Salmonowicz and Popowska, 2019;Seiler and Berendonk, 2012). The AR is conferred on bacteria by genes existing in the chromosomes and the MGEs (Baker-Austin et al., 2006). The maintenance and propagation of ARGs in bacteria is affected by environmental contaminants through co-selection mechanisms and the impact of heavy metals (HMs) contamination on ARGs has received much attention (Mazhar et al., 2021;Ye et al., 2017;Zhao et al., 2019Zhao et al., , 2020. ...
... Co-selection is the associated selection and expression of two or more resistance genes by bacteria even when exposed to only a selective trigger or stressor (Di Cesare et al., 2016). In addition to HMs (Baker-Austin et al., 2006;Gorovtsov et al., 2018;Maurya et al., 2020), other contaminants have been postulated to affect ARGs in the environment such as polyaromatic hydrocarbons (PAHs) (Gorovtsov et al., 2018), quaternary ammonium compounds (Wales and Davies, 2015), polychlorinated biphenyls (PCBs) (Gorovtsov et al., 2018), detergents (Wales and Davies, 2015;Ye et al., 2017), and anti-biofouling agents (biocides) (Wales and Davies, 2015;Ye et al., 2017). It is also postulated that ARB and ARGs may be higher in contaminated environmental media due to co-selection pressure (Cunningham et al., 2020). ...
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Heavy metals (HMs) contamination raises the expression of antibiotic resistance (AR) in bacteria through co-selection. Biochar application in composting improves the effectiveness of composting and the quality of compost. This improvement includes the elimination and reduction of antibiotic resistant genes (ARGs). The use of biochar in contaminated soils reduces the bioaccessibility and bioavailability of the contaminants hence reducing the biological and environmental toxicity. This decrease in contaminant bioavailability reduces contaminants induced co-selection pressure. Conditions which favour reduction in HMs bioavailable fraction (BF) appear to favour reduction in ARGs in compost and soil. Biochar can prevent horizontal gene transfer (HGT) and can eliminate ARGs carried by mobile genetic elements (MGEs). This effect reduces maintenance and propagation of ARGs. Firmicutes, Proteobacteria, and Actinobacteria are the major bacteria phyla identified to be responsible for dissipation, maintenance, and propagation of ARGs. Biochar application rate at 2-10% is the best for the elimination of ARGs. This review provides insight into the usefulness of biochar in the prevention of co-selection and reduction of AR, including challenges of biochar application and future research prospects.
... Exposure of bacteria to toxic levels of heavy metals and antibiotics, as a result of diverse anthropogenic activities and abuse of antibiotics have contributed to the emergence of bacterial resistant genes [5,6]. The co-existence of more than one antimicrobial such as antibiotics and heavy metals in microorganisms was due to the mechanisms of co-resistance and cross-resistance [7,8]. Co-resistance involves the presence of phenotypic resistance genes on a similar transmissible genetic element such as plasmids, transposons, and integrons which serve as physical vectors for the transmission of resistance genes from one microorganism to another conjugation [7]. ...
... The co-existence of more than one antimicrobial such as antibiotics and heavy metals in microorganisms was due to the mechanisms of co-resistance and cross-resistance [7,8]. Co-resistance involves the presence of phenotypic resistance genes on a similar transmissible genetic element such as plasmids, transposons, and integrons which serve as physical vectors for the transmission of resistance genes from one microorganism to another conjugation [7]. On the other hand, cross-resistance occurs when varying antimicrobial agentssuch as heavy metals and antibiotics target similar microorganisms through the same pathway, thereby resulting in cell death [7]. ...
... Co-resistance involves the presence of phenotypic resistance genes on a similar transmissible genetic element such as plasmids, transposons, and integrons which serve as physical vectors for the transmission of resistance genes from one microorganism to another conjugation [7]. On the other hand, cross-resistance occurs when varying antimicrobial agentssuch as heavy metals and antibiotics target similar microorganisms through the same pathway, thereby resulting in cell death [7]. Several authors have reported the adverse effect of metals such as cadmium, copper, lead and zinc on the microbiological balance of the soil, especially when present in high concentrations [9,10,11,12]. ...
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The study investigated the antibiogram profile and heavy metal tolerance of bacteria cultured from soils collected from metal scrap dumpsites in Benin City. Enumeration and characterization of bacterial isolates were carried out using standard procedures. The agar diffusion and Kirby-Bauer disc diffusion methods were used in determining the minimum inhibitory concentration (MIC) and the antibiotic susceptibility profile respectively. The total heterotrophic bacteria count ranged from 12.50 ± 3.44 to 22.50 ± 8.12 (×10 3 cfu/g), while the control sample has 34.50±11.57(×10 3 cfu/g), Six (6) bacterial isolates were identified; Bacillus subtilis, Micrococcus sp., Arthrobacter sp., Corynebacterium sp., Pseudomonas aureginosa and Escherichia coli. The Minimum inhibitory concentrations of the various isolates ranged from 5 to 25mg/l. Lead and cadmium showed the highest inhibition against bacterial isolates with MIC values between 5 and 10mg/l except Pseudomonas aeruginosa which tolerated cadmium at 15mg/l. Iron and zinc highly inhibited the isolates with MIC values ranging from 10 to 25mg/l. The bacteria isolates showed about 67% resistance to at least three test antibiotics with a multiple antibiotic resistance index of 0.3. The presence of resistant bacteria to heavy metal and antibiotics in the scrapyard soils could be critical to the health of the nearby residents as the scrapyard may act as a reserviour for the transmission of the antimicrobial agents .
... However, it cannot be disputed that human activities dramatically accelerate the proliferation and transmission of ARGs [4]. Apart from antibiotics, many other environmental pollutants (particularly metals) are increasingly recognized as important selective agents to promote the dissemination of ARGs in the environment [6,7]. ...
... Among the reported selective agents for ARGs, metals differ greatly from their organic counterparts due to their persistent nature and higher potential to accumulate to selecting levels [6]. As such, metals can be an even more important risk factor for the proliferation and transmission of ARGs in the environment than other selective agents [6,7]. ...
... Among the reported selective agents for ARGs, metals differ greatly from their organic counterparts due to their persistent nature and higher potential to accumulate to selecting levels [6]. As such, metals can be an even more important risk factor for the proliferation and transmission of ARGs in the environment than other selective agents [6,7]. In the past years, the potential correlations between metal level and ARG abundance or diversity in a variety of environments impacted by agriculture [8], animal husbandry, aquaculture [9,10], urbanization [11,12] and oil spill [13] have been studied extensively. ...
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Mining is among the human activities with widest environmental impacts, and mining-impacted environments are characterized by high levels of metals that can co-select for antibiotic resistance genes (ARGs) in microorganisms. However, ARGs in mining-impacted environments are still poorly understood. Here, we conducted a comprehensive study of ARGs in such environments worldwide, taking advantage of 272 metagenomes generated from a global-scale data collection and two national sampling efforts in China. The average total abundance of the ARGs in globally distributed studied mine sites was 1572 times per gigabase, being rivaling that of urban sewage but much higher than that of freshwater sediments. Multidrug resistance genes accounted for 40% of the total ARG abundance, tended to co-occur with multimetal resistance genes, and were highly mobile (e.g. on average 16% occurring on plasmids). Among the 1848 high-quality metagenome-assembled genomes (MAGs), 85% carried at least one multidrug resistance gene plus one multimetal resistance gene. These high-quality ARG-carrying MAGs considerably expanded the phylogenetic diversity of ARG hosts, providing the first representatives of ARG-carrying MAGs for the Archaea domain and three bacterial phyla. Moreover, 54 high-quality ARG-carrying MAGs were identified as potential pathogens. Our findings suggest that mining-impacted environments worldwide are underexplored hotspots of multidrug resistance genes.
... Rising sea surface temperatures and ocean pollution influence the abundance and geographic distribution of naturally occurring marine pathogens, such as Vibrio parahaemolyticus and Vibrio vulnificus (Baker-Austin et al., 2010). Therefore, the most likely consequences will be an increase in the frequency of Vibrio-associated diseases, as well as the spread of these infections to new, previously unaffected areas. ...
... On the other hand, in co-resistance, two or more resistance genes are physically linked and the genes responsible for two or more resistances are located together in a MGE, as plasmids, integrons or transposons, and could potentially propagate to other bacterial species through HGTs (Chapman, 2003;Seiler and Berendonk, 2012;Pal et al., 2017;Verma et al., 2019;Zou et al., 2021). Well-characterized mechanisms of cross-resistance and co-selection can be detailed reviewed in Baker-Austin and Collaborates (2006); Seiler and Berendonk (2012) and Imran and Collaborates (2019) (Baker-Austin et al., 2006;Seiler and Berendonk, 2012;Imran et al., 2019). ...
... HMs have been suggested to enhance selection for AR in the environment and vice versa through co-resistance, cross-resistance or coregulation of resistance pathways (Matyar et al., 2008;Zhang et al., 2021). In this regard, experimental evidence demonstrated a relationship between HMRGs and ARGs acquisition, both of which disseminated through the MGE Tennstedt et al., 2005;Baker-Austin et al., 2006;Szczepanowski et al., 2007;Graham et al., 2011;Knapp et al., 2011;Di Cesare et al., 2016a); these mechanisms were extensive review by Seiler andBerendonk, 2012 (Seiler and. Such elements, referred to as integrative and conjugative elements, are self-transmissible chromosomal MGE that encode a wide variety of genetic information: a characteristic set of core genes (for excision, circularization, conjugative transfer, and sitespecific integration) and cargo genes, which confer a wide range of phenotypes to their hosts, including antibiotic and HMs resistance (Wozniak and Waldor, 2010;Durrant et al., 2020). ...
Article
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Anthropogenic pollution has a huge impact on the water quality of marine ecosystems. Heavy metals and antibiotics are anthropogenic stressors that have a major effect on the health of the marine organisms. Although heavy metals are also associate with volcanic eruptions, wind erosion or evaporation, most of them come from industrial and urban waste. Such contamination, coupled to the use and subsequent misuse of antimicrobials in aquatic environments, is an important stress factor capable of affecting the marine communities in the ecosystem. Bivalves are important ecological components of the oceanic environments and can bioaccumulate pollutants during their feeding through water filtration, acting as environmental sentinels. However, heavy metals and antibiotics pollution can affect several of their physiologic and immunological processes, including their microbiome. In fact, heavy metals and antibiotics have the potential to select resistance genes in bacteria, including those that are part of the microbiota of bivalves, such as Vibrio spp. Worryingly, antibiotic-resistant phenotypes have been shown to be more tolerant to heavy metals, and vice versa, which probably occurs through co- and cross-resistance pathways. In this regard, a crucial role of heavy metal resistance genes in the spread of mobile element-mediated antibiotic resistance has been suggested. Thus, it might be expected that antibiotic resistance of Vibrio spp. associated with bivalves would be higher in contaminated environments. In this review, we focused on co-occurrence of heavy metal and antibiotic resistance in Vibrio spp. In addition, we explore the Chilean situation with respect to the contaminants described above, focusing on the main bivalves-producing region for human consumption, considering bivalves as potential vehicles of antibiotic resistance genes to humans through the ingestion of contaminated seafood.
... Zhang et al. (2017e) reported that 125 mg/L of zinc could increase ARGabundance during AD of swine manure. Heavy metals in feedstocks can increase the tolerance levels of microbes towards antibiotics (Baker-Austin et al., 2006), while metal resistance is well linked to antibiotic resistance (Zhang et al., 2020b). In such cases, the heavy metals pose a selection pressure on ARGs by transferring the co-occurred ARGs and metal resistance genes between bacteria via MGEs (Baker-Austin et al., 2006). ...
... Heavy metals in feedstocks can increase the tolerance levels of microbes towards antibiotics (Baker-Austin et al., 2006), while metal resistance is well linked to antibiotic resistance (Zhang et al., 2020b). In such cases, the heavy metals pose a selection pressure on ARGs by transferring the co-occurred ARGs and metal resistance genes between bacteria via MGEs (Baker-Austin et al., 2006). Nonetheless, monitoring heavy metals in feedstock for AD is not a common practice, while the presence of heavy metals can potentially influence ARG abundance. ...
Article
The overuse and inappropriate disposal of antibiotics raised severe public health risks worldwide. Specifically, the incomplete antibiotics metabolism in human and animal bodies contributes to the significant release of antibiotics into the natural ecosystems and the proliferation of antibiotic-resistant bacteria carrying antibiotic-resistant genes. The organic feedstocks used for anaerobic digestion are often highly-rich in residual antibiotics and antibiotic-resistant genes. Hence, understanding their fate during anaerobic digestion has become a significant research focus recently. Previous studies demonstrated that various process parameters could considerably influence the propagation of the antibiotic-resistant genes during anaerobic digestion and their transmission via land application of digestate. This review article scrutinizes the influences of process parameters on antibiotic-resistant genes propagation in anaerobic digestion and the inherent fundamentals behind their effects. Based on the literature review, critical research gaps and challenges are summarized to guide the prospects for future studies.
... Adaptive traits, like antibiotic resistance, can promote the maintenance of MGEs within host genomes and can also manifest through regulatory functional domains within the recombinases themselves. In particular, recombinases can contain domains regulating heavy metal resistance genes, known to often co-occur with ARGs (81,82). For example, we observed that MerR domains (83) are significantly enriched in certain serine recombi-nase occurring in transposable elements (Supplementary Figure S3C). ...
Article
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Prokaryotic Mobile Genetic Elements (MGEs) such as transposons, integrons, phages and plasmids, play important roles in prokaryotic evolution and in the dispersal of cargo functions like antibiotic resistance. However, each of these MGE types is usually annotated and analysed individually, hampering a global understanding of phylogenetic and environmental patterns of MGE dispersal. We thus developed a computational framework that captures diverse MGE types, their cargos and MGE-mediated horizontal transfer events, using recombinases as ubiquitous MGE marker genes and pangenome information for MGE boundary estimation. Applied to ∼84k genomes with habitat annotation, we mapped 2.8 million MGE-specific recombinases to six operational MGE types, which together contain on average 13% of all the genes in a genome. Transposable elements (TEs) dominated across all taxa (∼1.7 million occurrences), outnumbering phages and phage-like elements (<0.4 million). We recorded numerous MGE-mediated horizontal transfer events across diverse phyla and habitats involving all MGE types, disentangled and quantified the extent of hitchhiking of TEs (17%) and integrons (63%) with other MGE categories, and established TEs as dominant carriers of antibiotic resistance genes. We integrated all these findings into a resource (proMGE.embl.de), which should facilitate future studies on the large mobile part of genomes and its horizontal dispersal.
... Co-resistance refers to the presence of resistance to two or many classes of antibiotics/substances in the same bacterial strain. It refers to the presence of several resistance genes on the same genetic material, such as on plasmid or transposon [69,70]. For example, co-resistance for amoxicillin and ciprofloxacin in E. coli indicates that using one of these antibiotics will increase resistance for both amoxicillin and ciprofloxacin at same time [71]. ...
Article
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The overuse and misuse of antibiotics has contributed to the rise and spread of multidrug-resistant bacteria. To address this global public health threat, many countries have restricted the use of antibiotics as growth promoters and promoted the development of alternatives to antibiotics in human and veterinary medicine and animal farming. In food-animal production, acidifiers, bacteriophages, enzymes, phytochemicals, probiotics, prebiotics, and antimicrobial peptides have shown hallmarks as alternatives to antibiotics. This review reports the current state of these alternatives as growth-promoting factors for poultry and swine production and describes their mode of action. Recent findings on their usefulness and the factors that presently hinder their broader use in animal food production are identified by SWOT (strength, weakness, opportunity, and threat) analysis. The potential for resistance development as well as co- and cross-resistance with currently used antibiotics is also discussed. Using predetermined keywords, we searched specialized databases including Scopus, Web of Science, and Google Scholar. Antibiotic resistance cannot be stopped, but its spreading can certainly be hindered or delayed with the development of more alternatives with innovative modes of action and a wise and careful use of antimicrobials in a One Health approach.
... The phylogenetic tree was constructed by maximum-likelihood method (RAxML) based on the whole genomes of isolated strains. The donor G. apis strain W8126 is shown in red evidence has suggested that other elements (e.g., heavy metals) can select and stimulate the stabilization of aminoglycoside resistance genes [44]. ...
Article
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Background The spread of antibiotic resistance genes (ARGs) has been of global concern as one of the greatest environmental threats. The gut microbiome of animals has been found to be a large reservoir of ARGs, which is also an indicator of the environmental antibiotic spectrum. The conserved microbiota makes the honeybee a tractable and confined ecosystem for studying the maintenance and transfer of ARGs across gut bacteria. Although it has been found that honeybee gut bacteria harbor diverse sets of ARGs, the influences of environmental variables and the mechanism driving their distribution remain unclear. Results We characterized the gut resistome of two closely related honeybee species, Apis cerana and Apis mellifera, domesticated in 14 geographic locations across China. The composition of the ARGs was more associated with host species rather than with geographical distribution, and A. mellifera had a higher content of ARGs in the gut. There was a moderate geographic pattern of resistome distribution, and several core ARG groups were found to be prevalent among A. cerana samples. These shared genes were mainly carried by the honeybee-specific gut members Gilliamella and Snodgrassella. Transferrable ARGs were frequently detected in honeybee guts, and the load was much higher in A. mellifera samples. Genomic loci of the bee gut symbionts containing a streptomycin resistance gene cluster were nearly identical to those of the broad-host-range IncQ plasmid, a proficient DNA delivery system in the environment. By in vitro conjugation experiments, we confirmed that the mobilizable plasmids could be transferred between honeybee gut symbionts by conjugation. Moreover, “satellite plasmids” with fragmented genes were identified in the integrated regions of different symbionts from multiple areas. Conclusions Our study illustrates that the gut microbiota of different honeybee hosts varied in their antibiotic resistance structure, highlighting the role of the bee microbiome as a potential bioindicator and disseminator of antibiotic resistance. The difference in domestication history is highly influential in the structuring of the bee gut resistome. Notably, the evolution of plasmid-mediated antibiotic resistance is likely to promote the probability of its persistence and dissemination. Aghy2aoGk5W_8F1dgySKf9Video Abstract
... As for the clinical setting, RNA sequencing for transcriptomic characterization could be applied for the characterization of several infection states, including staphylococcal bacteremia, Lyme disease, candidiasis, tuberculosis (differentiation between latent and active infection states), and influenza [85]. In addition, another promising application of RNA-seq is in discriminating infectious versus non-infectious causes of acute disease [86]. ...
Article
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The burden of bacterial resistance to antibiotics affects several key sectors in the world, including healthcare, the government, and the economic sector. Resistant bacterial infection is associated with prolonged hospital stays, direct costs, and costs due to loss of productivity, which will cause policy makers to adjust their policies. Current widely performed procedures for the identification of antibiotic-resistant bacteria rely on culture-based methodology. However, some resistance determinants, such as free-floating DNA of resistance genes, are outside the bacterial genome, which could be potentially transferred under antibiotic exposure. Metagenomic and metatranscriptomic approaches to profiling antibiotic resistance offer several advantages to overcome the limitations of the culture-based approach. These methodologies enhance the probability of detecting resistance determinant genes inside and outside the bacterial genome and novel resistance genes yet pose inherent challenges in availability, validity, expert usability, and cost. Despite these challenges, such molecular-based and bioinformatics technologies offer an exquisite advantage in improving clinicians’ diagnoses and the management of resistant infectious diseases in humans. This review provides a comprehensive overview of next-generation sequencing technologies, metagenomics, and metatranscriptomics in assessing antimicrobial resistance profiles.
... Moreover, changes in the chemical and biological contents (including nitrogen, phosphorus, potassium, copper, zinc, arsenic, iron, doxycycline (DO), oxytetracycline (OTC), enrofloxacin (ENR), and florfenicol (FFC)) of sewage and waste may have different effects on the fate of plasmids and ARGs. Some previous studies investigated the effects of various physicochemical properties on ARGs (Baker-Austin et al. 2006;Zhang et al. 2017Zhang et al. , 2020Zhou et al. 2017), but most focused on the impact of a single factor on a specific type of ARG. Thus, the effects of multiple physicochemical properties on plasmids and ARGs in complex communities are not well understood. ...
Article
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Swine manure treatment plants are important reservoirs of plasmid-harboring antibiotic resistance genes (ARGs) and physicochemical contaminants, but the changes in the abundances of plasmids and ARGs, and their interactions with the physicochemical properties of manure, are still unclear. Thus, in the present study, plasmidome and metagenome analyses were conducted for samples collected at different stages in the swine manure treatment process. The results indicated that anaerobic digestion and aerobic digestion were the most efficient stages for reducing the abundances of ARGs in swine manure. However, the plasmids associated with ARGs were not effectively removed in these stages. Through the whole treatment process, the IncL/M, IncQ1, IncHI2A, IncA/C, and IncN plasmid groups had strong correlations (r > 0.8, P < 0.01) with most ARG types, thereby indicating that these plasmids play important roles in the persistence of ARGs in this environment. Furthermore, the pH, total nitrogen, total phosphorus, and four heavy metals (Cu, Zn, As, and Fe) significantly affected the abundances of seven ARG subtypes (tetB(P), ant(6)-Ia, tet44, aph(3′′)-Ib, mefB, tet(L), and tet(39)). In particular, florfenicol had the most positive correlations with ARGs. Our results indicated that nutrients, heavy metals, and antibiotics all contributed to the presence and persistence of plasmid-harboring ARGs. This study provides insights into the fate of plasmids and ARGs, and related factors during the swine manure treatment process, thereby facilitating the development of a new treatment technique for removing ARGs and reducing the public health risk associated with livestock production. Graphical abstract
... Among them, trace elements (Baker-Austin et al., 2006;Seiler and Berendonk, 2012), biocides (Capita et al., 2013;Pal et al., 2015), PAH and PCB Gorovtsov et al., 2018) could coselect for ARG. This phenomenon exemplifies the so-called 'cocktail effect' (see section 3.5). ...
... Considering that the abundance of ARGs is more relevant for transferring ARGs between non-pathogenic and pathogenic bacteria than the diversity of ARGs, the threshold of 0.034 mg kg −1 available Se is further discussed in this study. The role of metal(loid)s as co-selective pressures driving ARGs distribution has been widely demonstrated [66][67][68]. The present study showed that Se can induce a dual effect on ARGs pattern, unlike the positive correlation between metal(loid)s and ARGs reported in several previous studies [10,69]. ...
Article
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Background: Metal(loid)s can promote the spread and enrichment of antibiotic resistance genes (ARGs) in the environment through a co-selection effect. However, it remains unclear whether exposure of microorganisms to varying concentrations of selenium (Se), an essential but potentially deleterious metal(loid) to living organisms, can influence the migration and distribution of ARGs in forest soils. Results: Precisely 235 ARGs conferring resistance to seven classes of antibiotics were detected along a Se gradient (0.06-20.65 mg kg −1) across 24 forest soils. (flor)/(chlor)/(am)phenicol resistance genes were the most abundant in all samples. The total abundance of ARGs first increased and then decreased with an elevated available Se content threshold of 0.034 mg kg −1 (P = 2E−05). A structural equation model revealed that the dominant mechanism through which Se indirectly influences the vertical migration of ARGs is by regulating the abundance of the bacterial community. In addition, the methylation of Se (mediated by tehB) and the repairing of DNA damages (mediated by ruvB and recG) were the dominant mechanisms involved in Se resistance in the forest soils. The co-occurrence network analysis revealed a significant correlated cluster between Se-resistance genes, MGEs and ARGs, suggesting the co-transfer potential. Lelliottia amnigena YTB01 isolated from the soil was able to tolerate 50 μg mL −1 ampicillin and 1000 mg kg −1 sodium selenite, and harbored both Se resistant genes and ARGs in the genome. Conclusions: Our study demonstrated that the spread and enrichment of ARGs are enhanced under moderate Se pressure but inhibited under severe Se pressure in the forest soil (threshold at 0.034 mg kg −1 available Se content). The data generated in this pilot study points to the potential health risk associated with Se contamination and its associated influence on ARGs distribution in soil.
... ARGs are emerging environmental pollutants because of the continual discharge of both ARB, and pharmaceutical and chemical pollutants into the environment ). The diversity and the level of ARGs are related to the presence of ARB in the both sediments and waters of aquatic environments (Baker-Austin et al. 2006). In addition to industrial and hospital waste, a major contributing factor to the increasing levels of ARGs in the environment includes fecal pollution in urban regions (Newton et al. 2013;Karkman et al. 2019). ...
Article
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The spread of antimicrobial-resistant pathogens is a global health concern. Most studies report high levels of antimicrobial resistance genes (ARGs) in the aquatic environment; however, levels associated with sediments are limited. This study aimed to investigate the distribution of ARGs in the sediments and water of the Akaki river in Addis Ababa, Ethiopia. The diversity and abundance of 84 ARGs and 116 clinically important bacteria were evaluated from the sediments and water collected from five sites in the Akaki river. Most of the ARGs were found in the city close to anthropogenic activities. Water samples collected in the middle catchment of the river contained 71–75% of targeted ARGs, with genes encoding aminoglycoside acetyltransferase (aac(6)-Ib-cr), aminoglycoside adenylyl transferase (aadA1), β-lactamase (blaOXA-10), quinolone resistance S (qnrS), macrolide efflux protein A (mefA), and tetracycline resistance (tetA), were detected at all sampling sites. Much fewer ARGs were detected in all sediments, and those near the hospitals had the highest diversity and level. Despite the lower levels and diversity, there were no unique ARGs detected in the sediments that were also not detected in the waters. A wide range of clinically relevant pathogens were also detected in the Akaki river. The findings suggest that the water phase, rather than the sediments in the Akaki river, is a potential conduit for the spread of ARGs and antibiotic-resistant bacteria.
... In addition, the concomitant presence of non-antibiotic chemical stressors that have antimicrobial properties might contribute to the spread and selection of antibiotic resistance. Among them, trace elements (Baker-Austin et al., 2006;Seiler and Berendonk, 2012), biocides (Capita et al., 2013;Pal et al., 2015), PAH and PCB Gorovtsov et al., 2018) could co-select for ARG. This phenomenon exemplifies the so-called "cocktail effect" (see Section 3.5). ...
Chapter
Agricultural recycling of organic waste (OW) derived from urban, agricultural and agroindustrial sources is an essential sustainable development strategy. Yet repeated application of nutrient-laden OW in crop fields can also drastically boost contaminant levels in soil. This review focuses on the consideration of three categories of OW-borne contaminants, namely trace elements, organic contaminants and pathogens (including antibiotic resistance), in environmental assessments, chiefly involving life cycle assessment (LCA) and risk assessment (RA). The in-depth discussion also focuses on gaps between empirical knowledge and the models underlying these frameworks. Potential improvements to fill the identified gaps are proposed, including novel approaches and uses of existing approaches, while also featuring various levels of “readiness.” Finally, a comprehensive theoretical framework to assess OW recycling scenarios, combining complementary approaches and models, is proposed and exemplified.
... Jalal et al. [187] reported an improvement in antibacterial function of rifampicin (Rif)-loaded SLNs, against B. abortus, higher than unbound rifampicin by two folds. To avoid the side effects of Vancomycin (VAN), including renal failure and blood disorders such as neutropenia [188][189][190], Seedat et al. demonstrated that the co-encapsulation of multi-lipids and polymers could enhance the performance of VAN in lipid polymer hybrid nanoparticles (LPNs) by improving its entrapment as well as its release profile and antibacterial activity against both sensitive and resistant bacterial strains [191]. ...
Article
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Infectious diseases are among the major health issues of the 21st century. The substantial use of antibiotics over the years has contributed to the dissemination of multidrug resistant bacteria. According to a recent report by the World Health Organization, antibacterial (ATB) drug resistance has been one of the biggest challenges, as well as the development of effective long-term ATBs. Since pathogens quickly adapt and evolve through several strategies, regular ATBs usually may result in temporary or noneffective treatments. Therefore, the demand for new therapies methods, such as nano-drug delivery systems (NDDS), has aroused huge interest due to its potentialities to improve the drug bioavailability and targeting efficiency, including liposomes, nanoemulsions, solid lipid nanoparticles, polymeric nanoparticles, metal nanoparticles, and others. Given the relevance of this subject, this review aims to summarize the progress of recent research in antibacterial therapeutic drugs supported by nanobiotechnological tools.
... Further, there is nearly a complete lack of understanding of stormwater removal of ARGs, even though pathogens harboring ARGs pose the dual threat to public health of increased and less treatable waterborne illness. There is also the possibility that biofilters could serve as a hotspot for ARG proliferation due to the prevalence of biofilms in these systems (fostering horizontal gene transfer) and introduction from sewage of selective and co-selective factors such as heavy metals and antibiotics (Baker-Austin et al., 2006). ...
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Green stormwater infrastructure systems, such as biofilters, provide many water quality and other environmental benefits, but their ability to remove human pathogens and antibiotic resistance genes (ARGs) from stormwater runoff is not well documented. In this study, a field scale biofilter in Southern California (USA) was simultaneously evaluated for the breakthrough of a conservative tracer (bromide), conventional fecal indicators, bacterial and viral human-associated fecal source markers (HF183, crAssphage, and PMMoV), ARGs, and bacterial and viral pathogens. When challenged with a 50:50 mixture of untreated sewage and stormwater (to mimic highly contaminated storm flow) the biofilter significantly removed (p < 0.05) 14 of 17 microbial markers and ARGs (in descending order of concentration reduction, ermB (2.5 log(base 10) reduction) > Salmonella (2.3) > adenovirus (1.9) > coliphage (1.5) > crAssphage (1.2) > E. coli (1.0) ∼ 16S rRNA genes (1.0) ∼ fecal coliform (1.0) ∼ intl1 (1.0) > Enterococcus (0.9) ∼ MRSA (0.9) ∼ sul1 (0.9) > PMMoV (0.7) > Entero1A (0.5)). No significant removal was observed for GenBac3, Campylobacter, and HF183. From the bromide data, we infer that 0.5 log-units of attenuation can be attributed to the dilution of incoming stormwater with water stored in the biofilter; removal above this threshold is presumably associated with non-conservative processes, such as physicochemical filtration, die-off, and predation. Our study documents high variability (>100-fold) in the removal of different microbial contaminants and ARGs by a field-scale stormwater biofilter operated under transient flow and raises further questions about the utility of human-associated fecal source markers as surrogates for pathogen removal.
... N 2 , Ar, and O 2 (2.7%, 1.6%, and 0.15%, respectively): *370 ppm H 2 O and a pressure of 980 Pa with a high level of radiation that reaches a total UV >200 nm fluencies of about 4.92 · 102 kJ m -2 for the unprotected sample (de Vera et al., 2019). Furthermore, no studies to date have addressed the mechanisms involved in the spread of antibiotic resistance such as, for instance, metal resistance genes (MRGs) as co-selectors of ARGs in the absence of antibiotic selective pressure (Baker-Austin et al., 2006), in extraterrestrial environments. Thus, no information is available about how ARGs and MRGs interact and evolve in the complete absence of anthropogenic pollution and in the outer reaches of a Marslike environment. ...
Article
The spread of antibiotic resistance is becoming a serious global health concern. Numerous studies have been done to investigate the dynamics of antibiotic resistance genes (ARGs) in both indoor and outdoor environments. Nonetheless, few studies are available about the dynamics of the antibiotic resistome (total content of ARGs in the microbial cultures or communities) under stress in outer space environments. In this study, we aimed to experimentally investigate the dynamics of ARGs and metal resistance genes (MRGs) in Kombucha Mutualistic Community (KMC) samples exposed to Mars-like conditions simulated during the BIOMEX experiment outside the International Space Station with analysis of the metagenomics data previously produced. Thus, we compared them with those of the respective non-exposed KMC samples. The antibiotic resistome responded to the Mars-like conditions by enriching its diversity with ARGs after exposure, which were not found in non-exposed samples (i.e., tet and van genes against tetracycline and vancomycin, respectively). Furthermore, ARGs and MRGs were correlated; therefore, their co-selection could be assumed as a mechanism for maintaining antibiotic resistance in Mars-like environments. Overall, these results highlight the high plasticity of the antibiotic resistome in response to extraterrestrial conditions and in the absence of anthropogenic stresses.
... Anthropogenic-derived heavy metals are significant environmental contaminants (Baker-Austin et al., 2006). Although some heavy metals, such as Cu and Zn, are essential in trace amounts for the growth of organisms, they are toxic in excess (Xiong et al., 2015). ...
Article
Heavy metals are a group of anthropogenic contaminants in estuary ecosystems. Bacteria in estuaries counteract the highly concentrated metal toxicity through metal resistance genes (MRGs). Presently, metagenomic technology is popularly used to study MRGs. However, an easier and less expensive method of acquiring MRG information is needed to deepen our understanding of the fate of MRGs. Thus, this study explores the feasibility of using a machine learning approach-namely, random forests (RF)-to predict MRG abundance based on the 16S rRNA amplicon sequenced datasets from subtropical estuaries in China. Our results showed that the total MRG abundance could be predicted by RF models using bacterial composition at different taxonomic levels. Among them, the relative abundance of bacterial phyla had the highest predicted accuracy (71.7 %). In addition, the RF models constructed by bacterial phyla predicted the abundance of six MRG types and nine MRG subtypes with substantial accuracy (R 2 > 0.600). Five bacterial phyla (Firmicutes, Bacteroidetes, Patescibacteria, Armatimo-nadetes, and Nitrospirae) substantially determined the variations in MRG abundance. Our findings prove that RF models can predict MRG abundance in South China estuaries during the wet season by using the bacterial composition obtained by 16S rRNA amplicon sequencing.
... Although the concentration of antibiotics in the environment is much less than the therapeutic doses, these are sufficient to induce antimicrobial resistance in environmental microbiota (8)(9)(10). Compounding concerns are the release of many other compounds in the environment which can co-select resistance to antibiotics (11)(12)(13). ...
Article
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The spatial distribution of clinically important antibiotic resistant bacteria (ARB) and associated genes is important to identify environmental distribution of contamination and ‘hotspots’ of antimicrobial resistance (AMR). We conducted an integrated survey of AMR in drinking water, wastewater and surface water (rivers and ponds) in three settings in Bangladesh: rural households, rural poultry farms, and urban food markets. Spatial mapping was conducted via geographic information system (GIS) using ArcGIS software. Samples (n = 397) were analyzed for the presence of extended-spectrum β-lactamase-producing Escherichia coli (ESBL-Ec), carbapenem-resistant E. coli (CR-Ec) and resistance genes (blaCTX-M-1, blaNDM-1). In rural households, 5% of drinking water supply samples tested positive for ESBL-Ec, and a high proportion of wastewater, pond and river water samples were positive for ESBL-Ec (90%, 76%, and 85%, respectively). In poultry farms, 10% of drinking water samples tested positive for ESBL-Ec compared to a high prevalence in wastewater, pond and river water (90%, 68%, and 85%, respectively). CR-Ec prevalence in household wastewater and pond water was relatively low (8% and 5%, respectively) compared to river water (33%). In urban areas, 38% of drinking water samples and 98% of wastewater samples from markets tested positive for ESBL-Ec while 30% of wastewater samples tested positive for CR-Ec. Wastewaters had the highest concentrations of ESBL-Ec, CR-Ec, blaCTXM-1 and blaNDM-1 and these were significantly higher in urban compared to rural samples (p < 0.05). ESBL-Ec is ubiquitous in drinking water, wastewater and surface water bodies in both rural and urban areas of Bangladesh. CR-Ec is less widespread but found at a high prevalence in wastewater discharged from urban food markets and in rural river samples. Surveillance and monitoring of antibiotic resistant organisms and genes in waterbodies is an important first step in addressing environmental dimensions of AMR.
... Bacteria reproduce much more rapidly than parasites and can share resistance genes horizontally. Co-resistance, or resistance to more than one class of antibacterials that is often transmitted on mobile elements such as plasmids, and cross-resistance, in which a target used by multiple antibacterials is altered, can both result in resistance to multiple types of antibacterials [53]. With MDAazithromycin, it is possible that the benefits may only be Table 4 Evidence for antibacterial resistance (ABR) following MDA-azithromycin MDA mass drug administration, MORDOR Macrolides Oraux pour Réduire les Décès avec un Oeil sur la Résistance, PRET the Partnership for Rapid Elimination of Trachoma, RCTs cluster randomized trials, TANA Trachoma amelioration in Northern Amhara ...
Article
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Background: Mass drug administration (MDA) is a strategy to improve health at the population level through widespread delivery of medicine in a community. We surveyed the literature to summarize the benefits and potential risks associated with MDA of antibacterials, focusing predominantly on azithromycin as it has the greatest evidence base. Main body: High-quality evidence from randomized controlled trials (RCTs) indicate that MDA-azithromycin is effective in reducing the prevalence of infection due to yaws and trachoma. In addition, RCTs suggest that MDA-azithromycin reduces under-five mortality in certain low-resource settings that have high childhood mortality rates at baseline. This reduction in mortality appears to be sustained over time with twice-yearly MDA-azithromycin, with the greatest effect observed in children < 1 year of age. In addition, observational data suggest that infections such as skin and soft tissue infections, rheumatic heart disease, acute respiratory illness, diarrheal illness, and malaria may all be treated by azithromycin and thus incidentally impacted by MDA-azithromycin. However, the mechanism by which MDA-azithromycin reduces childhood mortality remains unclear. Verbal autopsies performed in MDA-azithromycin childhood mortality studies have produced conflicting data and are underpowered to answer this question. In addition to benefits, there are several important risks associated with MDA-azithromycin. Direct adverse effects potentially resulting from MDA-azithromycin include gastrointestinal side effects, idiopathic hypertrophic pyloric stenosis, cardiovascular side effects, and increase in chronic diseases such as asthma and obesity. Antibacterial resistance is also a risk associated with MDA-azithromycin and has been reported for both gram-positive and enteric organisms. Further, there is the risk for cross-resistance with other antibacterial agents, especially clindamycin. Conclusions: Evidence shows that MDA-azithromycin programs may be beneficial for reducing trachoma, yaws, and mortality in children < 5 years of age in certain under-resourced settings. However, there are significant potential risks that need to be considered when deciding how, when, and where to implement these programs. Robust systems to monitor benefits as well as adverse effects and antibacterial resistance are warranted in communities where MDA-azithromycin programs are implemented.
... Another important route for the spread of sil operon is co-selection under the pressure of antibiotics, especially βlactams. 33,34 Previous works have reported the relationship of silE and CTX-M-15 in E. coli strains from human and avian. 35 Another study showed higher prevalence of silC gene in bla NDM-1 -positive Enterobacteriaceae than that in bla CTM-M-15 -producing strains and in susceptible strains. ...
Article
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Purpose: Due to the extensive consumption of silver-containing compound, silver resistance spreads among gram-negative pathogens and is regarded as a great public problem. In this study, we investigated silver resistance mechanisms and antibiotic resistance genes co-harbored with sil operon among gram-negative pathogens isolated from wound samples. Methods: A total of 193 strains of gram-negative pathogens were collected from wound samples between 2018 and 2020 in Xiangya hospital. Silver resistance was obtained by broth microdilution method. The silver resistance mechanisms and the prevalence, genetic environments, and coexistence with antibiotic resistance genes of sil operon were investigated by polymerase chain reaction (PCR) and whole genome sequencing (WGS). Results: Among 193 strains, nine strains (4.7%) were resistant to Ag+ and assigned to the following species: Klebsiella pneumoniae (n = 5) and Enterobacter hormaechei (n = 4). WGS confirmed that 24 strains carried the entire sil operon, including the four Ag+-resistant E. hormaechei and 20 Ag+-susceptible strains, while PCR failed to detect some sil genes, especially silE, due to sequence variations. In seven strains, Tn7 transposon was identified in the upstream of sil operon. Spontaneous mutants resistant to Ag+ were induced in 15 out of 20 Ag+-susceptible strains, including K. pneumoniae strains belonged to high-risk groups (ST11 and ST15). The sil-positive strains harbored various antibiotic resistance genes, including bla ESBL and bla ApmC. WGS revealed that a single mutation in cusS gene and loss of major porins conferred silver resistance in the five K. pneumoniae strains. Conclusion: Our findings emphasize the cryptic silver resistance is prevalent among Enterobacteriaceae with sil operon or with the combination of cus operon and major porin loss and increase the understanding of the prevalence of sil operon with antibiotic resistance genes, especially bla ESBL and bla ApmC.
... (2) replacing the target of drugs and metals (antibiotics: chloramphenicol, β-lactams; and metals: As, Hg); (3) using active pumps to discharge drugs and metals (antibiotics: chloramphenicol, tetracycline, β-lactams; and metals: As, Cd, Co, Cu, Ni, Zn); (4) target replacement (antibiotics: ciprofloxacin, rifampicin, trimethoprim, β-lactams; and metals: Cu, Hg, Zn,); and (5) isolation of drugs and metals (antibiotic: coumermycin A; and metals: Cd, Cu, Zn) (Baker-Austin et al. 2006). Among the metal resistance genes, Cu resistance gene is the most abundant gene, followed by genes encoding resistances to Zn, Ni, Cd, Co, Fe, Mn, As, Ag, Te, Hg, Pb, Mn, Cr, Au, Ga, Sb, V, Se, and Bi, respectively (Pal et al. 2014). ...
... Furthermore, the presence of residues of antimicrobials and metals selects bacterial strains resistant to antimicrobials and tolerant to metals, respectively. The metals allow the coselection of antimicrobial-resistant strains by mechanisms of coresistance and cross-resistance (Baker-Austin et al., 2006;Tamhankar and Stålsby Lundborg, 2019). In metal-contaminated environments, the occurrence of antimicrobial resistance genes (ARG) and the co-selection and horizontal gene transfer (HGT) of plasmid-mediated ARGs have already been described (Yang et al., 2017;Imran et al., 2019). ...
Article
Multidrug-resistant (MDR) Escherichia coli isolates (n = 50) were recovered from aquatic ecosystems, which presented high counts of E. coli and metal values within the recommended range. These isolates showed different multidrug resistance profiles, highlighting the resistance to extended-spectrum cephalosporins, polymyxins, and fluoroquinolones. Several antimicrobial resistance genes (ARGs) were found, spotlighting the presence of at least one β-lactamase-encoding gene in each E. coli isolate. Substitutions in the quinolone resistance-determining regions and the two-component systems involving PhoP/PhoQ and PmrA/PmrB were also found. The metal tolerance gene rcnA (nickel and cobalt efflux pump) was the most prevalent. In this regard, 94% of E. coli isolates presented the co-occurrence of at least one ARG and metal tolerance gene. Furthermore, virulence genes and genetic diversity were found among MDR E. coli isolates. The emergence of potentially pathogenic isolates exhibiting multidrug resistance and metal tolerance emerged as a global health problem at the human-animal-environment interface.
... Antimicrobial resistance (AMR) poses serious threats to public health globally. The abuse of non-antibiotic chemicals greatly promotes the emergence and spread of AMR (Baker-Austin et al., 2006;Li et al., 2016;Wang et al., 2020). Since the coronavirus pandemic in 2020, the use of disinfectants (e.g., surface cleaners, sanitizers) has increased dramatically across the world, which is expected to increase AMR in pathogenic microbes in the coming years (Mahoney et al., 2021). ...
Article
The usage of quaternary ammonium compounds (QACs) as disinfectants has increased dramatically since the outbreak of COVID-19 pandemic, leading to potentially accelerated emergence of antibiotic resistance. Long-term exposure to subinhibitory level QACs can lead to multidrug resistance, but the contribution of mutagenesis to resistance evolution is obscure. In this study, we subcultured E. coli K-12 under subinhibitory (0.25× and 0.5× Minimum Inhibitory Concentration, MIC) or inhibitory (1× and 2 × MIC) concentrations of benzalkonium chloride (BAC, mono-chained) or didecyldimethylammonium chloride (DDAC, twin-chained) for 60 days. The sensitivity of QAC-adapted cells to five typical antibiotics decreased significantly, and in particular, the MIC of rifampicin increased by 85 times. E. coli adapted faster to BAC but developed 20–167% higher antibiotic resistance with 56% more mutations under DDAC exposure. The broader mutations induced by QACs, including negative regulators (acrR, marR, soxR, and crp), outer membrane proteins and transporters (mipA and sbmA), and RNA polymerase (rpoB and rpoC), potentially contributed to the high multi-drug resistance. After QACs stresses were removed, the phenotypic resistance induced by subinhibitory concentrations of QACs was reversible, whereas that induced by inhibitory concentrations of QACs was irreversible. The different patterns and molecular mechanism of antibiotic resistance induced by BAC and DDAC is informative to estimating the risks of broader QACs present at varied concentrations in the environment.
... Heavy metals like copper, zinc, nickel, arsenic, cadmium, and mercury have been reported to provide a co-selection pressure for antibiotic resistance of proteobacteria and actinobacteria [144][145][146][147]. The co-selection mechanism mainly involves co-regulation, co-resistance, and cross-resistance [148]. When antibiotics and heavy metals exist in the environment, bacteria may form resistance through the coresistance mechanism, while through cross-resistance mechanisms, bacteria can activate the efflux pump protein and thus become resistant to heavy metals and antibiotics. ...
Article
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Human health is threatened by antibiotic-resistant bacteria and their related infections, which cause thousands of human deaths every year worldwide. Surface waters are vulnerable to human activities and natural processes that facilitate the emergence and spread of antibiotic-resistant bacteria in the environment. This study evaluated the pathways and drivers of antimicrobial resistance (AR) in surface waters. We analyzed antibiotic resistance healthcare-associated infection (HAI) data reported to the CDC’s National Healthcare Safety Network to determine the number of antimicrobial-resistant pathogens and their isolates detected in healthcare facilities. Ten pathogens and their isolates associated with HAIs tested resistant to the selected antibiotics, indicating the role of healthcare facilities in antimicrobial resistance in the environment. The analyzed data and literature research revealed that healthcare facilities, wastewater, agricultural settings, food, and wildlife populations serve as the major vehicles for AR in surface waters. Antibiotic residues, heavy metals, natural processes, and climate change were identified as the drivers of antimicrobial resistance in the aquatic environment. Food and animal handlers have a higher risk of exposure to resistant pathogens through ingestion and direct contact compared with the general population. The AR threat to public health may grow as pathogens in aquatic systems adjust to antibiotic residues, contaminants, and climate change effects. The unnecessary use of antibiotics increases the risk of AR, and the public should be encouraged to practice antibiotic stewardship to decrease the risk.
Article
Antibiotic resistance and heavy metal pollution in water bodies are becoming more prominent concerns throughout the world, since heavy metal tolerance in bacteria is a contributing factor to the emergence of antimicrobial resistance. Recently, researchers established a link between heavy metal exposure and antibiotic resistance in bacteria; in both cases, similar mechanisms exist to allow bacteria to survive in adverse settings while producing antibiotic resistance. Several co-resistance mechanisms may be found on the same plasmid or genetic element, or they may be found on different chromosomal materials. Heavy metals are released into the environment by several industrial and domestic activities, which pollutes and contaminates land and water bodies. Heavy metal concentrations in bodies of water are continuing to grow, exposing the present bacterial variety to tolerance mechanisms and allowing them to develop a larger degree of resistance to heavy metals over time. When these bacteria are exposed to antibiotics in the future, they will activate and express previously developed mechanisms, which will enable them to survive at high dosages with relative ease in the future. Antibiotic and heavy metal resistance in aquatic bacteria is increasing, which may have ramifications for environmental, therapeutic, and drug development investigations, among other things.
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In this study, a multi-metal-tolerant natural bacterial isolate Providencia rettgeri strain KDM3 from an industrial effluent in Mumbai, India, showed high cadmium (Cd) tolerance. Providencia rettgeri grew in the presence of more than 100 ppm (880 μM) Cd (LD50 = 100 ppm) and accumulated Cd intracellularly. Following Cd exposure, a comparative proteome analysis revealed molecular mechanisms underlying Cd tolerance. Among a total of 69 differentially expressed proteins (DEPs) in Cd-exposed cells, de novo induction of ahpCF operon proteins and L-cysteine/L-cystine shuttle protein FliY was observed, while Dps and superoxide dismutase proteins were overexpressed, indicating upregulation of a robust oxidative stress defense. ENTRA1, a membrane transporter showing homology to heavy metal transporter, was also induced de novo. In addition, the protein disaggregation chaperone ClpB, trigger factor, and protease HslU were also overexpressed. Notably, 46 proteins from the major functional category of energy metabolism were found to be downregulated. Furthermore, the addition of P. rettgeri to Cd-spiked soil resulted in a significant reduction in the Cd content [roots (11%), shoot (50%), and grains (46%)] of the rice plants. Cd bioaccumulation of P. rettgeri improved plant growth and grain yield. We conclude that P. rettgeri, a highly Cd-tolerant bacterium, is an ideal candidate for in-situ bioremediation of Cd-contaminated agricultural soils.
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Manmade urban lakes are potential tourism site as well as a source of livelihood. urban lake Saheb Bandh in Purulia district were being used by the local communities residing nearby for various purposes such as fishing purposes, ecotourism, waste disposal, idol immersion, swimming, bathing and drinking purposes. Thus, Saheb Bandh Lake situated between 23º29'42"N latitude and 86º21'37"E longitude of Purulia district, West Bengal, India was assessed to study bacteriological characteristics of the lake water for quality assessment of drinking and recreational purposes. Studies on the abundance and distribution of heterotrophic bacterial communities of Total Coliform (TC) bacteria and Fecal Coliform (FC) bacteria revealed a distinct seasonal variation of their population with relatively higher values in summer and monsoon season and lower during winter. All the samples obtained from the lake were positive with respect to the coliform occurrence, though the count was variable ranged between 0.05×10 3 MPN/100 ml. and 8.75×10 3 MPN/100 ml. in TC whereas in FC it was ranged between 0.01×10 4 MPN/100 ml. and 5.65×10 4 MPN/100 ml. Highest proportion of indicator coliforms was found in the water samples collected from the littoral zone where anthropogenic disturbances taken place. The results showed that the most of the water samples lying in category III and category IV and 0% sample lying in category I. The results allow to conclude that none of the studied water samples was fit for drinking purposes in view of high coliform count, could be used for bathing, swimming and recreational purposes. This result has important implications for municipality and local inhabitants that use the water of this lake for various purposes.
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Culturable bacterial diversity and co-occurrence of heavy metal and antibiotic resistance were investigated from the water and sediments along the course of the Teesta River, in the Eastern Himalayas. Water and sediment samples collected from six sampling points during the monsoon and winter seasons were subjected to analysis of physico-chemical parameters, heavy metal contamination and antibiotic tolerance. The culturable bacterial diversity established by application of bacterial culture and 16S rRNA gene sequencing, ascertained the majority belonged to Proteobacteria, Actinobacteria, Firmicutes, Bacteroidetes and Deinococcus-Thermus. Among the 5 phyla, Proteobacteria and Actinobacteria were the dominant phyla present in both water and sediment samples, whereas Bacteroidetes, Firmicutes and Deinococcus-Thermus were unique to particular sites. The Shannon index indicated that the bacterial richness was more in the water column as compared to sediment. From the total of 245 isolates, 69 genera were identified. Heavy metal tolerance and antibiotic resistance profiles showed some isolates to be tolerant to high levels of heavy metals and multiple antibiotics indicating a major concern in terms of river ecosystem serving as a pool for dissemination of such resistant genes. The antibiotic resistance and heavy metal contamination diversified along the human-impacted downstream sites, endorsing the contribution of anthropogenic factors. The present report on bacterial diversity and the associated metal and antibiotics tolerance among bacteria is the first of its kind on Teesta River, the only major river system flowing through the state of Sikkim and parts of North Bengal.
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Heavy metal pollution and the potential for co-selection of resistance to antibiotics in the environment is growing concern. However, clear associations between heavy metals and antibiotic resistance in river systems have not been developed. Here we investigated relationships between total and bioavailable heavy metals concentrations; metal resistance gene (MRG) and antibiotic resistance gene (ARG) abundances; mobile genetic elements; and the composition of local bacterial communities in low and high metal polluted rivers in UK and India. The results indicated that MRGs conferring resistance to cobalt (Co) and nickel (Ni) (rcnA), and Co, zinc (Zn), and cadmium (Cd) (czcA), and ARGs conferring resistance to carbapenem and erythromycin were the dominating resistant genes across the samples. The relative MRGs, ARGs, and integrons abundances tended to increase at high metal polluted environments, suggesting high metals concentrations have a strong potential to promote metal and antibiotic resistance by horizontal gene transmission and affecting bacterial communities, leading to the development of multi-metal and multi-antibiotic resistance. Network analysis demonstrated the positive and significant relationships between MRGs and ARGs as well as the potential for integrons playing a role in the co-transmission of MRGs and ARGs (r > 0.80, p < 0.05). Additionally, the major host bacteria of various MRGs and ARGs that could be accountable for greater MRGs and ARGs levels at high metal polluted environments were also identified by network analysis. Spearman's rank-order correlations and RDA analysis further confirm relationships between total and bioavailable heavy metals concentrations and the relative MRG, ARG, and integron abundances, as well as the composition of related bacterial communities (r > 0.80 (or < −0.80), p < 0.05). These findings are critical for assessing the possible human health concerns associated with metal-driven antibiotic resistance and highlight the need of considering metal pollution for developing appropriate measures to control ARG transmission.
Thesis
Le concept One Health suppose que les santés humaine, animale et environnementale sont interconnectées. Il promeut une approche holistique et transdisciplinaire pour appréhender les problèmes de santé publique. Les risques infectieux et la résistance aux antibiotiques sont des préoccupations majeures du concept One Health. L'environnement est souvent relégué au second plan lors de la mise en place d'approches One Health. Ce travail de recherche vise à combler le manque de connaissances quant à la diffusion des bacilles à Gram négatif commensaux et pathogènes (BGN-CP) dans l'environnement. Escherichia coli, Klebsiella pneumoniae et Pseudomonas aeruginosa sont trois espèces bactériennes associées à l'Homme qui acquièrent facilement des déterminants de résistance aux antibiotiques. Ces BGN-CP contaminent l'environnement, principalement via les eaux usées et les activités agricoles. Dans ce travail, nous avons étudié le devenir des BGN-CP dans les écosystèmes aquatiques des plaines alluviales. E. coli, K. pneumoniae et P. aeruginosa sont largement dispersées dans les hydrosystèmes. Leur survie, influencée par les facteurs abiotiques et biotiques, est généralement faible dans l'environnement. Toutefois, certaines conditions favorisent leur survie, voire leur prolifération dans des écosystèmes spécifiques. Certaines zones humides peuvent constituer des réservoirs environnementaux de BGN-CP. L’environnement joue un rôle mineur dans la contamination par les BGN-CP dans les pays à revenus élevés, où la transmission interhumaine prédomine. En revanche, la situation peut être beaucoup plus complexe dans les pays à revenus faibles et intermédiaires où les compartiments humain et environnement sont plus connectés. Bien que l'environnement est supposé jouer un rôle limité dans la rétro contamination de l'Homme par les BGN-CP dans les pays à revenus élevés, sa prise en compte dans l'approche One Health est indispensable car les changements induits par l'Anthropocène pourraient accroître le risque sanitaire pour les populations humaines.
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Rising antibiotic resistance rates in H. pylori are associated with increased rates of treatment failure. Understanding how stressors impact antibiotic resistance may shed light on the development of future treatment strategies.
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Rapid development of aquaculture industry and increasing demand of various inputs (especially antibiotics), are suspected to promote the occurrence and spread of ARGs in aquaculture related environments. However, the occurrences of ARGs under different freshwater aquaculture practices are rarely known. Here, we investigated the seasonal profiles of the main ARGs, intI1 and bacteria in waters from three kinds of predominant freshwater aquaculture practices around the Honghu Lake (China), as well as their co-occurrences and interrelationships with antibiotics, heavy metals and general water quality. The results indicate that quinolone resistance genes (qnrB), tetracycline resistance genes (tetB and tetX) and sulfonamide resistance genes (sul1 and sul2) were the top five predominant ARGs with seasonal variations of abundance. Fish ponds were of the highest absolute abundances of tested ARGs than the other two modes. Crayfish ponds and their adjacent ditches shared similar ARGs profile. Different subtypes of ARGs belonging to the same class of resistance were varied in abundances. Some bacteria were predicted to carry different ARGs, which indicating multi-antibiotic resistances. Moreover, the combined environmental factors (antibiotics, heavy metals and water quality) partially shaped the profiles of ARGs and bacteria composition. Overall, this study provides new comprehensive understanding on the characterization of ARGs contamination in different freshwater aquaculture practices from the perspectives of environmental chemistry, microbiology and ecology. The results would benefit the optimization of aquaculture practices toward environmental integrity and sustainability.
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Manure application increases the transfer risk of antibiotic resistance to farmland. Especially, its impact remains unclear when it occurs in arsenic (As)-contaminated paddy soils, which is considered as a global environmental problem. In this work, we investigated the fate of antibiotic resistance genes (ARGs) in As-antibiotic co-contaminated paddy soils under the application of manure from different sources (pig manure, cow dung, and chicken manure). Differences in the aliphatic carbon and electron-donating capacities of these dissolved organic matters (DOMs) regulated the transformation of iron and As by both biotic and abiotic processes. The regulation by pig manure was stronger than that by cow dung and chicken manure. DOM regulation increased the abundance of As-related functional genes (arsC, arrA, aioA, and arsM) in the soil and accelerated the transformation of As speciation, the highest proportion of As(III) being 45–61%. Meanwhile, the continuous selection pressure provided by the highly toxic As(III) increased the risk of ARGs and mobile genetic elements (MGEs) via horizontal gene transfer. As-resistant bacteria, including Bacillus, Geobacter, and Desulfitobacterium, were finally considered as potential host bacteria for ARGs and MGEs. In summary, this study clarified the synergistic mechanism of As-antibiotic on the fate of ARGs in co-contaminated paddy soils, and provided practical guidance for the proper application of organic fertilizers.
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Genome of Mycetocola spongiae MSC19T, a novel marine sponge-associated Actinobacteria isolated from the Mariana Trench sponge Cacospongia mycofijiensis, was sequenced. The genome has one circular chromosome of 3,196,754 bp, with an average GC content of 66.43 mol%, and 2887 coding sequences. Gene annotation shows that M. spongiae MSC19T possesses series of genes related to adaptation to deep-sea environmental stresses including cold shock, heat shock, osmotic stress and oxidative stress. Genes encoding for heavy metal resistance, multidrug resistance and multiple natural product biosynthesis which are crucial for survival in the extreme environment are also detected in the genome. The potentials to synthesize kinds of vitamins and eukaryotic-like proteins indicates the possible nutrient exchange and mutual recognization between M. spongiae MSC19T and its sponge host. The genome provides insights into the stress resistance and ecological fitness of bacterial symbionts in the deep-sea sponge holobionts.
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Antimicrobial resistance (AMR), especially antibiotic resistance, has posed a huge threat to public health. Moreover, heavy metal, another significant contaminant, can accelerate the generation and dissemination of AMR. Thus, the method and mechanism of AMR removal under heavy metal stress need to be elucidated urgently. Adsorption has been proved to be an important means to deal with AMR pollution. However, there is still a lack of systematic reviews on decontaminating the combined pollution of AMR and heavy metal by adsorption. With this in mind, this review introduces two types of adsorbents, carbon-based materials (biochar and graphene oxide) and clay minerals, which can remove antibiotic resistance genes (ARGs) efficiently even under heavy metal stress. Besides, we summarize the crucial factors affecting the variations of ARGs, and the mechanisms of ARGs removal by two materials under the influences of these factors are proposed. Then, the pathways of two materials to decrease ARGs by reducing heavy metal co-selection and altering microbial communities under heavy metal stress are emphasized. Finally, the bottlenecks of the research on reducing ARGs by these adsorbents and the prior study directions in the future are described in detail. To sum up, the review offers new insight into the mitigation of AMR and heavy metal pollution and facilitates the progress of feasible methods for the removal of ARGs and heavy metal.
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A cellulose-based hydrogel with synergistic therapeutic effect was prepared by a one-pot method. The hydrogel had hydroxyethyl cellulose (HEC) as a framework and epichlorohydrin (EPI) as a cross-linking agent. Cationic-β-cyclodextrin (C-β-CD) was homogeneously embedded in the grid of the cross-linked structure. Zinc oxide nanoparticles (ZnO NPs) and menthol were used to provide analgesic and bactericidal effects. Menthol was uniformly loaded onto the hydrogel matrix by the addition of C-β-CD and increased the solubility of menthol in water. ZnO NPs were synthesized by in situ hydrothermal treatment. The positively charged group of C-β-CD and the active hydroxyl group of HEC were used to distribute the ZnO NPs uniformly on the hydrogel matrix without significant agglomeration. The hydrogel had a smoothly ordered and compact morphology. It exhibited adequate mechanical, swelling, water retention and oxygen permeability properties in tests. In addition, the hydrogel had an efficient bactericidal effect. Release experiments showed that the encapsulation of menthol by C-β-CD allowed for a slow release of menthol. Biocompatibility tests had shown that the hydrogel was non-toxic to normal human cells.
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Antimicrobial resistance (AMR) is a global health crisis that poses a great threat to modern medicine. Effective prevention strategies are urgently required to slow the emergence and further dissemination of AMR. Given the availability of data sets encompassing hundreds or thousands of pathogen genomes, machine learning (ML) is increasingly being used to predict resistance to different antibiotics in pathogens based on gene content and genome composition. A key objective of this work is to advocate for the incorporation of ML into front-line settings but also highlight the further refinements that are necessary to safely and confidently incorporate these methods. The question of what to predict is not trivial given the existence of different quantitative and qualitative laboratory measures of AMR. ML models typically treat genes as independent predictors, with no consideration of structural and functional linkages; they also may not be accurate when new mutational variants of known AMR genes emerge. Finally, to have the technology trusted by end users in public health settings, ML models need to be transparent and explainable to ensure that the basis for prediction is clear. We strongly advocate that the next set of AMR-ML studies should focus on the refinement of these limitations to be able to bridge the gap to diagnostic implementation.
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Sewage sludge (SS), also termed “biosolids”, is a derivative of handling processes carried out for sewage sludge. Sewage sludge is a basin of organic material and nutrients, so it encompasses a possible substrate for selection of probable circumstances. Much water, a high amount of organic matter and the presence of high amounts of pathogenic microorganisms in solids are removed during preliminary sedimentation. The disposal of sewage sludge to agricultural soil is one of the best disposal alternatives. The quality of sewage and nature of processes used for the treatment show the characteristics of sewage sludge. Because there is a presence of various “organic and inorganic plant nutrients” in sewage sludge it may be a best alternative for fertilizer, but due to the presence of various toxic elements its use is often restricted. Amendment of sewage sludge to soil mutates its physico‐chemical properties and soil microbial properties. Crop yields in soil amended with sewage sludge are usually higher than that of well‐fertilized controls. Metals bioavailability elevates in sewage sludge amended soil at extreme amounts of application for many years. There is a difference in the quality of the primary sludge and secondary sludge as well. Methods of stabilization of sludge treatment and disposal methods are dependent upon its composition. The composition of sewage sludge is highly uneven and it depends upon many aspects such as seasons, the technology behind different wastewater treatment plants and the specificity of pollutant source areas, etc. The aim of this chapter is to review the accessible information on the application of sewage sludge on the fertility of soil and resulting effects on the production of plants.
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Hot springs are thought to be potential repositories for opportunistic infections, such as antibiotic-resistant strains. However, there is a scarcity of information on the mechanisms of antibiotic resistance gene (ARG) uptake, occurrence, and expression in thermophilic bacteria. Furthermore, because the genesis and proliferation of ARGs in environmental microorganisms are unknown, the research on antibiotic resistance profiles and probable mechanisms in thermophilic bacteria will become increasingly important. The goals of this study are to explore bacterial diversity, antibiotic and heavy metal resistance, and the prevalence and presence of ARG and metal resistance gene (MRG) in Geobacillus species. The 16S rRNA sequencing was used to determine the culturable bacterium diversity of 124 isolates. Standard Kirby Bauer Disc Diffusion and tube dilution procedures were used to determine antibiotic sensitivity and minimum inhibitory concentration (MIC). The tube dilution method was also used to check metal tolerance. To detect ARG and heavy MRG (HMRG), whole genome sequencing studies of the type species of the genus Geobacillus and five randomly selected Geobacillus species were performed. Graph Pad Prism and XLSTAT were used to perform statistical analyses such as ANOVA, EC50 analysis, and principal component analysis (PCA). The phylum Firmicutes and the genus Geobacillus dominated the culture-dependent bacterial diversity. Surprisingly, all thermophilic isolates, i.e., Geobacillus species, were sensitive to at least 10 different antibiotics, as evidenced by the lack of ARGs in whole genome sequencing analysis of numerous Geobacillus species. However, some of these isolates were resistant to at least five different heavy metals, and whole genome sequencing revealed the presence of MRGs in these thermophilic bacteria. The thermophilic genus Geobacillus is generally antibiotic sensitive, according to this study. In contrast, heavy metal is tolerated by them. As a result, it is possible that ARGs and MRGs do not coexist in these bacteria living in hot springs.
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Although the enrichment of antibiotic resistance genes (ARGs) in diverse organic soils have been explored, understanding of the ecological processes governing the composition of ARGs in long-term organically fertilized soils still remains limited across typical agricultural regions. Thus, the distribution and assembly of ARG profile in three typical agricultural soils (black soil, fluvo-aquic soil, and red soil) under long-term contrasting fertilization regimes (chemical-only vs organic-only) were investigated using high-throughput qPCR (HT-qPCR). The application of organic manure significantly increased the abundance and number of ARGs across soils, as compared to those with chemical fertilizer. Organic manure application enriched the abundance of mobile genetic elements (MGEs), which were positively associated with ARGs. In addition, it is long-term organic fertilizer that enriched the number and abundance of opportunist and specialist ARGs in the fluvo-aquic and red soils, but not black soils. The number and abundance of most generalist ARGs did not change significantly among different fertilization or soil types. The assembly process of the ARG profiles tends to be more deterministic in organically fertilized soils than in chemically fertilized soils. These results suggest that long-term organic fertilizer application may contribute to the persistence and health risk of the soil antibiotic resistomes (especially specialist ARGs).
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A chromosomal gene (mdrL) was found in Listeria monocytogenes L028, showing a high degree of similarity with multidrug efflux transporters of the major facilitator superfamily (family 2). An allele-substituted mutant of this gene failed to pump out ethidium bromide and presented lower minimal inhibitory concentrations of macrolides, cefotaxime and heavy metals. This is the first multidrug efflux pump described in Listeria.
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Antibiotic resistance among avian bacterial isolates is common and is of great concern to the poultry industry. Approximately 36% (n = 100) of avian, pathogenic Escherichia coli isolates obtained from diseased poultry exhibited multiple-antibiotic resistance to tetracycline, oxytetracycline, streptomycin, sulfonamides, and gentamicin. Clinical avian E. coli isolates were further screened for the presence of markers for class 1 integrons, the integron recombinase intI1 and the quaternary ammonium resistance gene qacEΔ1, in order to determine the contribution of integrons to the observed multiple-antibiotic resistance phenotypes. Sixty-three percent of the clinical isolates were positive for the class 1 integron markers intI1 and qacEΔ1. PCR analysis with the conserved class 1 integron primers yielded amplicons of approximately 1 kb from E. coli isolates positive for intI1 and qacEΔ1. These PCR amplicons contained the spectinomycin-streptomycin resistance gene aadA1. Further characterization of the identified integrons revealed that many were part of the transposon Tn21, a genetic element that encodes both antibiotic resistance and heavy-metal resistance to mercuric compounds. Fifty percent of the clinical isolates positive for the integron marker gene intI1 as well as for the qacEΔ1 and aadA1 cassettes also contained the mercury reductase gene merA. The correlation between the presence of the merA gene with that of the integrase and antibiotic resistance genes suggests that these integrons are located in Tn21. The presence of these elements among avian E. coli isolates of diverse genetic makeup as well as in Salmonella suggests the mobility of Tn21 among pathogens in humans as well as poultry.
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Bacterial DNA gyrases are type II topoisomerases made up of two A subunits and two B subunits. Coumarins are carbohydrate-containing antibiotics that inhibit topoisomerases II by competing with ATP for binding to the enzymes. High resistance to coumarins is produced in bacterial species by mutations in gyrB, the gene encoding subunit B. We have found an unusual mechanism of resistance to coumarins in Escherichia coli. This mechanism is exhibited by cells containing the wild-type gyrB, or its 5' half, in high copy number. Since homologous mutant gyrB (coumermycin resistant) truncated genes did not confer drug resistance at all under the same conditions, we propose that this mechanism of resistance is due to drug sequestration by the overproduced wild-type GyrB polypeptides. A corollary of this is that the amino half of GyrB is required and sufficient to fashion the ATP-binding domain of DNA gyrase, a conclusion that was further supported by mapping three independent coumarin-resistant mutations at Arg-136 of GyrB. Just upstream of this residue there is a glycine-rich sequence highly conserved in all topoisomerases II, which seems to be a good candidate for the actual ATP-binding site.
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The penicillinase plasmids, a series of extrachromosomal resistance factors in Staphylococcus aureus, were found to carry determinants of resistance to a series of inorganic ions as well as resistance to penicillin and, in some cases, erythromycin. Most of the ions involved were inhibitory but not lethal to the bacteria; the resistance markers conferred an increase in resistance by comparison with susceptible organisms of between 3- and 100-fold, depending on the ion involved. Separate genetic loci for resistance to arsenate, arsenite, lead, cadmium, mercuric, and bismuth ions were demonstrated. Resistance to antimony and resistance to zinc were also found but were not separated genetically from resistance to arsenite and cadmium, respectively. The ion resistance markers appeared to form a cluster on the plasmid, with no other known marker within it. Naturally occurring plasmids were observed that lacked one or more of these ion resistance markers, as well as penicillinase-negative strains that were resistant to one or more of the ions. The patterns of markers carried by these various strains may provide some understanding of the evolution of a plasmid linkage group.
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Bacterial isolates from the drinking water system of an Oregon coastal community were examined to assess the association of metal tolerance with multiple antibiotic resistance. Positive correlations between tolerance to high levels of Cu2+, Pb2+, and Zn2+ and multiple antibiotic resistance were noted among bacteria from distribution waters but not among bacteria from raw waters. Tolerances to higher levels of Al3+ and Sn2+ were demonstrated more often by raw water isolates which were not typically multiple antibiotic resistant. A similar incidence of tolerance to Cd2+ was demonstrated by isolates of both water types and was not associated with multiple antibiotic resistance. These results suggest that simultaneous selection phenomena occurred in distribution water for bacteria which exhibited unique patterns of tolerance to Cu2+, Pb2+, and Zn2+ and antibiotic resistance.
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Escherichia coli K-12 OST3410 was isolated previously as a stable cyclohexane-tolerant mutant derived from cyclohexane-sensitive strain JA300. A plasmid which provides cyclohexane tolerance to strain JA300 was isolated from the OST3410 genomic library. Subcloning and sequence analysis showed that the plasmid contained the robA gene, whose gene product was reported to bind specifically to the right border of oriC. We observed that the robA gene on the multicopy plasmid generally increased the organic solvent tolerance of several E. coli strains. We also observed an increase in the organic solvent tolerance of JA300 carrying the lac-robA fusion gene on a low-copy plasmid by isopropyl-beta-D-thiogalactopyranoside induction. Strain JA300 carrying the multicopy robA plasmid also showed an increase in resistance to a number of unrelated antibiotics and heavy metal ions, and the spectrum of resistance was significantly similar to that of the soxS-overexpressing strain.
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Plant-associated pseudomonads are commonly exposed to copper bactericides, which are applied to reduce the disease incidence caused by these bacteria. Consequently, many of these bacteria have acquired resistance or tolerance to copper salts. We recently conducted a survey of 37 copper-resistant (Cur) Pseudomonas spp., including P. cepacia, P. fluorescens, P. syringae, and P. viridiflava, and found that a subset of the P. syringae strains showed a dramatic increase in exopolysaccharide (EPS) production on mannitol-glutamate medium containing CuSO4 at 250 micrograms/ml. A modified carbazole assay indicated that the EPS produced on copper-amended media contained high levels of uronic acids, suggesting that the EPS was primarily alginic acid. Uronic acids extracted from selected strains were further confirmed to be alginate by demonstrating their sensitivity to alginate lyase and by descending paper chromatography following acid hydrolysis. Subinhibitory levels of arsenate, cobalt, lithium, rubidium, molybdenum, and mercury did not induce EPS production, indicating that alginate biosynthesis is not induced in P. syringae cells exposed to these heavy metals. A 200-kb plasmid designated pPSR12 conferred a stably mucoid phenotype to several P. syringae recipients and also increased their resistance to cobalt and arsenate. A cosmid clone constructed from pPSR12 which conferred a stably mucoid phenotype to several P. syringae strains but not to Pseudomonas aeruginosa was obtained. Results obtained in this study indicate that some of the signals and regulatory genes for alginate production in P. syringae differ from those described for alginate production in P. aeruginosa.
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In a survey of 640 human subjects, a subgroup of 356 persons without recent exposure to antibiotics demonstrated that those with a high prevalence of Hg resistance in their intestinal floras were significantly more likely to also have resistance to two or more antibiotics. This observation led us to consider the possibility that mercury released from amalgam ("silver") dental restorations might be a selective agent for both mercury- and antibiotic-resistant bacteria in the oral and intestinal floras of primates. Resistances to mercury and to several antibiotics were examined in the oral and intestinal floras of six adult monkeys prior to the installation of amalgam fillings, during the time they were in place, and after replacement of the amalgam fillings with glass ionomer fillings (in four of the monkeys). The monkeys were fed an antibiotic-free diet, and fecal mercury concentrations were monitored. There was a statistically significant increase in the incidence of mercury-resistant bacteria during the 5 weeks following installation of the amalgam fillings and during the 5 weeks immediately following their replacement with glass ionomer fillings. These peaks in incidence of mercury-resistant bacteria correlated with peaks of Hg elimination (as high as 1 mM in the feces) immediately following amalgam placement and immediately after replacement of the amalgam fillings. Representative mercury-resistant isolates of three selected bacterial families (oral streptococci, members of the family Enterobacteriaceae, and enterococci) were also resistant to one or more antibiotics, including ampicillin, tetracycline, streptomycin, kanamycin, and chloramphenicol. While such mercury- and antibiotic-resistant isolates among the staphylococci, the enterococci, and members of the family Enterobacteriaceae have been described, this is the first report of mercury resistance in the oral streptococci. Many of the enterobacterial strains were able to transfer mercury and antibiotic resistances together to laboratory bacterial recipients, suggesting that the loci for these resistances are genetically linked. Our findings indicate that mercury released from amalgam fillings can cause an enrichment of mercury resistance plasmids in the normal bacterial floras of primates. Many of these plasmids also carry antibiotic resistance, implicating the exposure to mercury from dental amalgams in an increased incidence of multiple antibiotic resistance plasmids in the normal floras of nonmedicated subjects.
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Antimicrobial resistance is more widespread than can be accounted for as being a consequence of the selection pressure caused by the use of antibiotics alone. In this study, we tested the hypothesis that a high mercury content in feces might select for mercury-resistant bacteria and thus for antimicrobial resistance linked to mercury resistance. Three subject groups with different exposures to dental amalgam fillings were compared. None of the subjects had taken antimicrobial agents during the three preceding months or longer. The group exposed to dental amalgam (n = 92) had 13 times more mercury in feces than the group that had never been exposed to amalgam (n = 43) and the group whose amalgam fillings had been removed (n = 56). No significant differences in either mercury resistance or antibiotic resistance in the fecal aerobic gram-negative flora of these subject groups were seen. The following antimicrobial resistance frequencies were detected with a replica plating method: > or = 1% resistance was seen in 40% of the subjects for ampicillin, 14% of the subjects for cefuroxime, 6% of the subjects for nalidixic acid, 14% of the subjects for trimethoprim, 19% of the subjects for sulfamethoxazole, and 25% of the subjects for tetracycline. The amount of mercury in feces derived from amalgam was not selective for any resistance factors in aerobic gram-negative bacteria, but antimicrobial resistance was widespread even among healthy subjects with no recent exposure to antibiotics.
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Bacterial plasmids encode resistance systems for toxic metal ions including Ag+, AsO2-, AsO4(3-), Cd2+, CO2+, CrO4(2-), Cu2+, Hg2+, Ni2+, Pb2+, Sb3+, TeO3(2-), Tl+, and Zn2+. In addition to understanding of the molecular genetics and environmental roles of these resistances, studies during the last few years have provided surprises and new biochemical mechanisms. Chromosomal determinants of toxic metal resistances are known, and the distinction between plasmid resistances and those from chromosomal genes has blurred, because for some metals (notably mercury and arsenic), the plasmid and chromosomal determinants are basically the same. Other systems, such as copper transport ATPases and metallothionein cation-binding proteins, are only known from chromosomal genes. The largest group of metal resistance systems function by energy-dependent efflux of toxic ions. Some of the efflux systems are ATPases and others are chemiosmotic cation/proton antiporters. The CadA cadmium resistance ATPase of gram-positive bacteria and the CopB copper efflux system of Enterococcus hirae are homologous to P-type ATPases of animals and plants. The CadA ATPase protein has been labeled with 32P from gamma-32P-ATP and drives ATP-dependent Cd2+ uptake by inside-out membrane vesicles. Recently isolated genes defective in the human hereditary diseases of copper metabolism, Menkes syndrome and Wilson's disease, encode P-type ATPases that are more similar to the bacterial CadA and CopB ATPases than to eukaryote ATPases that pump different cations. The arsenic resistance efflux system transports arsenite, using alternatively either a two-component (ArsA and ArsB) ATPase or a single polypeptide (ArsB) functioning as a chemiosmotic transporter. The third gene in the arsenic resistance system, arsC, encodes an enzyme that converts intracellular arsenate [As (V)] to arsenite [As (III)], the substrate of the efflux system. The three-component Czc (Cd2+, Zn2+, and CO2+) chemiosmotic efflux pump of soil microbes consists of inner membrane (CzcA), outer membrane (CzcC), and membrane-spanning (CzcB) proteins that together transport cations from the cytoplasm across the periplasmic space to the outside of the cell. Finally, the first bacterial metallothionein (which by definition is a small protein that binds metal cations by means of numerous cysteine thiolates) has been characterized in cyanobacteria.
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Gram-negative fecal bacterial from three longitudinal Hg exposure experiments and from two independent survey collections were examined for their carriage of the mercury resistance (mer) locus. The occurrence of antibiotic resistance was also assessed in both mercury-resistant (Hgr) and mercury-susceptible (Hgs) isolates from the same collections. The longitudinal studies involved exposure of the intestinal flora to Hg released from amalgam "silver" dental restorations in six monkeys. Hgr strains were recovered before the installation of amalgams, and frequently these became the dominant strains while amalgams were installed. Such persistent Hgr strains always carried the same mer locus throughout the experiments. In both the longitudinal and survey collections, certain mer loci were preferentially associated with one genus, whereas other mer loci were recovered from many genera. In general, strains with any mer locus were more likely to be multiresistant than were strains without mer loci; this clustering tendency was also seen for antibiotic resistance genes. However, the association of antibiotic multiresistance with mer loci was not random; regardless of source, certain mer loci occurred in highly multiresistant strains (with as many as seven antibiotic resistances), whereas other mer loci were found in strains without any antibiotic resistance. The majority of highly multiresistant Hgr strains also carried genes characteristic of an integron, a novel genetic element which enables the formation of tandem arrays of antibiotic resistance genes. Hgr strains lacking antibiotic resistance showed no evidence of integron components.
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The transposon Tn21 and a group of closely related transposons (the Tn21 family) are involved in the global dissemination of antibiotic resistance determinants in gram-negative facultative bacteria. The molecular basis for their involvement is carriage by the Tn21 family of a mobile DNA element (the integron) encoding a site-specific system for the acquisition of multiple antibiotic resistance genes. The paradigm example, Tn21, also carries genes for its own transposition and a mercury resistance (mer) operon. We have compiled the entire 19,671-bp sequence of Tn21 and assessed the possible origins and functions of the genes it contains. Our assessment adds molecular detail to previous models of the evolution of Tn21 and is consistent with the insertion of the integron In2 into an ancestral Tn501-like mer transposon. Codon usage analysis indicates distinct host origins for the ancestral mer operon, the integron, and the gene cassette and two insertion sequences which lie within the integron. The sole gene of unknown function in the integron, orf5, resembles a puromycin-modifying enzyme from an antibiotic producing bacterium. A possible seventh gene in the mer operon (merE), perhaps with a role in Hg(II) transport, lies in the junction between the integron and the mer operon. Analysis of the region interrupted by insertion of the integron suggests that the putative transposition regulator, tnpM, is the C-terminal vestige of a tyrosine kinase sensor present in the ancestral mer transposon. The extensive dissemination of the Tn21 family may have resulted from the fortuitous association of a genetic element for accumulating multiple antibiotic resistances (the integron) with one conferring resistance to a toxic metal at a time when clinical, agricultural, and industrial practices were rapidly increasing the exposure to both types of selective agents. The compendium offered here will provide a reference point for ongoing observations of related elements in multiply resistant strains emerging worldwide.
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Forty isolates of Bradyrhizobium sp. (cajanus) were isolated from the nodules of pigeon pea plants grown in fields receiving petrochemical industrial wastewater for the past 12 years and characterized using standard methods. The heavy metal analysis of field soil and treated wastewater showed their presence in varying concentrations. All isolates showed resistance to one or more metals at concentrations >200 g/ml. Multiple metal resistance was a common phenomenon in these isolates. There was no correlation between extractable soil metal concentration and the ability of the isolates to tolerate metal salts in their growth medium as evidenced from their minimum inhibitory concentration (MIC). However, high incidence of metal resistance and the multiple nature of resistance