Figure - available from: Frontiers in Cellular and Infection Microbiology
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A schematic representation showing the interplay of different factors influence in antimicrobial resistance. (p)ppGpp increases the efficiency of HGT, AMR cassette acquisition through IntlI and upregulates the expression of various components of the efflux pumps. Non-coding small RNAs (sRNAs) play a major role in post-transcriptional regulation of gene expression. This includes, negatively regulated targets of MgrR involved in LPS modification (sensitivity to Polymyxin B); SdsR, repress the expression of tolC, the gene encoding the OMP of many multidrug resistance efflux pumps; SdsR also base-pair with mutS mRNA to repair the DNA after exposure to β-lactams; SprX (a.k.a. RsaOR) influence resistance to glycopeptides by downregulating the SpoVG; DsrA activates the expression of MdtE, which increases efflux system to antibiotic such as oxacillin, cloxacillin, erythromycin, novobiocin etc. RybB negatively influences the expression of csgD transcription, which is the master regulator of biofilm formation. sRNAs strongly interact with the co-factor Hfq, which enhances sRNA stability and facilitates base-pairing of sRNAs with multiple target mRNAs. Small RNAs are typed in dark brown. Solid arrows indicate activating interactions and T-arrows indicate inhibiting interactions.
Source publication
Antimicrobial resistance (AMR) in bacteria is an important global health problem affecting humans, animals, and the environment. AMR is considered as one of the major components in the “global one health”. Misuse/overuse of antibiotics in any one of the segments can impact the integrity of the others. In the presence of antibiotic selective pressur...
Citations
... The study of antimicrobial resistance (AMR) has revealed that bacteria possess an array of genetic and phenotypic adaptations that enable resistance to antibiotics [8][9][10]. These include transmissible plasmids, biofilm formation, swarming behaviour, and the persistence of dormant cells [11]. ...
This study investigates the antimicrobial properties of methanol and hexane extracts from three marine sponges in Tobago: Iotrochota birotulata, Cliona caribbaea, and Topsentia ophiraphidites. The extracts were tested against Staphylococcus aureus and Escherichia coli using disc diffusion assays. Among the three species, Cliona caribbaea (Sponge B) demonstrated the strongest antimicrobial activity, surpassing the control antibiotic Amoxiclav. Gas chromatography-mass spectrometry (GC-MS) identified key bioactive compounds such as Hexadecenoic acid methyl ester, Methyl oleate, and Methyl stearate, contributing to the observed effectiveness. In contrast, extracts from Iotrochota birotulata and Topsentia ophiraphidites showed minimal to no antimi-crobial activity, with methanol extracts being particularly ineffective. These findings highlight Cliona caribbaea as a promising source of bioactive compounds for developing alternatives to traditional antibiotics. ARTICLE HISTORY
... Antimicrobial resistance (AMR) is a natural phenomenon caused by the expression of a variety of resistance genes (Ramamurthy et al., 2022). The development of resistance is exacerbated by the high demand for antimicrobials, their misuse, and unnecessary prescriptions (Belachew et al., 2021). ...
Introduction
Antimicrobial resistance (AMR) poses a significant threat to global public health. The One Health approach, which integrates human, animal, and environmental health, highlights the roles of agricultural and hospital settings in the propagation of AMR. This study aimed to analyze the resistome and gut microbiome composition of individuals from a high-intensity animal husbandry area in the western region of Santa Catarina, Southern Brazil, who were subsequently admitted to the University Hospital in the city of Florianopolis, located in the eastern part of the same state.
Methods
Rectal swab samples were collected upon admission and discharge. Metagenomic sequencing and resistome analysis were employed to identify antimicrobial resistance genes (ARGs) and their associated bacterial taxa. Additionally, the impact of the hospital environment on the resistome and microbiome profiles of these patients was assessed.
Results
A total of 247 genetic elements related to AMR were identified, with 66.4% of these elements present in both admission and discharge samples. Aminoglycoside resistance genes were the most prevalent, followed by resistance genes for tetracyclines and lincosamides. Notably, unique resistance genes, including dfrF and mutations in gyrB , were identified at discharge. ARGs were associated with 55 bacterial species, with Lactobacillus fermentum , harboring the ermB gene. (MLSB), detected in both admission and discharge samples. The most prevalent bacterial families included Mycobacteriaceae , Enterobacteriaceae, and Bacteroidaceae . Among these, Mycobacteriaceae was the most abundant, with ARGs primarily associated with mutations in the 16S rRNA gene, RNA polymerase subunits, and gyrases.
Discussion
The study revealed a high prevalence of genes related to aminoglycoside and tetracycline resistance, with a notable increase in certain resistance determinants at discharge, likely influenced by extended antimicrobial use. The presence of mcr genes, associated with colistin resistance, in both admission and discharge samples from a single patient highlights a concerning trend in AMR, particularly in relation to animal husbandry. These findings underscore the substantial impact of antimicrobial use on resistance development and the complex dynamics of the resistome in hospital settings. They also emphasize the influence of local factors, such as intensive animal production, on resistance patterns and advocate for ongoing surveillance and policy development to manage multidrug-resistant bacteria eVectively.
... The formation of biofilms is influenced by different bacterial species and various external environmental factors. Biofilms can enhance bacterial resistance to harsh environments and increase their tolerance to antibiotics (Ramamurthy et al., 2022;Michaelis and Grohmann, 2023). The phenomenon of enhanced biofilm formation associated with the p3R-IncX3 plasmid carrying bla NDM-5 has been documented, indicating that it can boost the biofilm formation ability of certain host bacteria (Ma et al., 2020). ...
Escherichia coli (E. coli) serves as a critical indicator microorganism for assessing the prevalence and dissemination of antibiotic resistance, notably harboring various antibiotic-resistant genes (ARGs). Among these, the emergence of the blaNDM gene represents a significant threat to public health, especially since carbapenem antibiotics are vital for treating severe infections caused by Gram-negative bacteria. This study aimed to characterize the antibiotic resistance features of blaNDM-5-positive E. coli strains isolated from waterfowl in several regions of China and elucidate the dissemination patterns of the blaNDM-5 gene. We successfully isolated 103 blaNDM-5-positive E. coli strains from 431 intestinal fecal samples obtained from waterfowl across five provincial-level units in China, with all strains exhibiting multidrug resistance (MDR). Notably, the blaNDM-5 gene was identified on plasmids, which facilitate efficient and stable horizontal gene transfer (HGT). Our adaptability assays indicated that while the blaNDM-5-positive plasmid imposed a fitness cost on the host bacteria, the NDM-5 protein was successfully induced and purified, exhibiting significant enzymatic activity. One strain, designated DY51, exhibited a minimum inhibitory concentration (MIC) for imipenem of 4 mg/L, which escalated to 512 mg/L following exposure to increasing imipenem doses. This altered strain demonstrated stable resistance to imipenem alongside improved adaptability, correlating with elevated relative expression levels of the blaNDM-5 and overexpression of efflux pumps. Collectively, this study highlights the horizontal dissemination of the blaNDM-5 plasmid among E. coli strains, confirms the associated fitness costs, and provides insights into the mechanisms underlying the stable increase in antibiotic resistance to imipenem. These findings offer a theoretical framework for understanding the dissemination dynamics of blaNDM-5 in E. coli, which is essential for developing effective strategies to combat carbapenem antibiotic resistance.
... In order to survive, bacteria have to constantly adapt to their surrounding environment by undergoing physiological and metabolic changes. Such adaptations may also affect their susceptibility to antibiotics or disinfectants, and have an impact on the success of antimicrobial therapies [1,2]. For this reason, it is very important to study the efficacy of different strategies under environmental conditions that mimic potential therapeutic settings. ...
Environmental cues sometimes have a direct impact on phage particle stability, as well as bacterial physiology and metabolism, having a profound effect on phage infection outcome. Here, we explore the impact of temperature on the interplay between phage Kayvirus rodi (phiIPLA-RODI) and its host, Staphylococcus aureus. Our results show that phiIPLA-RODI is a more effective predator at room (25 °C) compared to body temperature (37 °C) against planktonic cultures of several strains with varying degrees of phage susceptibility. This result differs from most known examples of temperature-dependent phage infection, in which optimum infection is correlated with the host growth rate. Further characterization of this phenomenon was carried out with strains IPLA15 and IPLA16, whose respective MICs were 7 log units and a 1-log unit higher at 37 °C than at 25 °C. Our results demonstrated that the phage also had a greater impact at room temperature during biofilm development and for the treatment of preformed biofilms. There was no difference in phage adsorption between the two temperatures for strain IPLA16. Conversely, adsorption of phiIPLA-RODI to IPLA15 was reduced at 37 °C compared to 25 °C. Moreover, confocal microscopy analysis indicated that the biofilm matrix of both strains has a greater content of PIA/PNAG at 37 °C than at 25 °C. Regarding infection parameters, we observed longer duration of the lytic cycle at 25 °C for both strains, and infection of IPLA15 by phiIPLA-RODI resulted in a smaller burst size at 37 °C than at 25 °C. Finally, we also found that the rate of phage resistant mutant selection was higher at 37 °C for both strains. Altogether, this information highlights the impact that bacterial responses to environmental factors have on phage-host interactions. Moreover, phage phiIPLA-RODI appears to be a highly effective candidate for biofilm disinfection at room temperature, while its efficacy in biofilm-related infections will require combination with other antimicrobials.
... The URT harbors a diverse microbiome, including bacteria, fungi, and viruses; studies show that 11 disruptions in the microbiome can lead to dysbiosis, creating an environment conducive to the 12 selection and spread of AMR genes 1 demonstrated that viral infections could induce changes in the microbiota that favor the 18 selection of pathogenic bacteria capable of acquiring resistance 5 . 19 AMR in the URT was a growing concern due to widespread antibiotic use in treating respiratory 20 infections even before the COVID-19 pandemic. ...
The COVID-19 pandemic has raised concerns about antimicrobial resistance (AMR), especially in the context of secondary bacterial infections. This study investigates the impact of SARS-CoV-2 infection on the resistome of the upper respiratory tract (URT) using a metagenomic next-generation sequencing (mNGS) approach. Samples from 48 SARS-CoV-2-infected individuals and 47 healthy individuals from Central India were analyzed to assess variations in AMR gene profiles. Our results revealed significant differences in AMR gene diversity and abundance between the two groups. SARS-CoV-2 samples exhibited greater alpha diversity (Chao1 index) and higher variability, as evidenced by PCA and PCoA analyses, which showed distinct clustering. Additionally, 24 AMR gene families were significantly more abundant in the SARS-CoV-2 group. These gene families conferred resistance against 20 different drug classes, including macrolides, beta-lactams, and aminoglycosides. Notably, AMR genes linked to ESKAPE pathogens were more prevalent in the SARS-CoV-2 group. These findings highlight the potential role of SARS-CoV-2 in driving changes in the URT resistome, with implications for managing secondary infections and guiding antibiotic stewardship in future pandemics.
Keywords: SARS-CoV-2, antimicrobial resistance, resistome, upper respiratory tract, metagenomics, ESKAPE pathogens, antibiotic resistance.
... The interplay between genetic mechanisms and selection pressure in AMR is complex and multifaceted. On the one hand, bacteria adapt to host defense systems and antimicrobial agents through diverse mechanisms (e.g., structural changes, enzymatic processes, and gene regulation) [145]. On the other hand, mobile genetic elements (e.g., plasmids and transposons) disseminate ARGs, and non-genetic factors (e.g., transcriptional heterogeneity) facilitate the development of genetic drug resistance [146]. ...
Antimicrobial resistance (AMR), frequently considered a major global public health threat, requires a comprehensive understanding of its emergence, mechanisms, advances, and implications. AMR’s epidemiological landscape is characterized by its widespread prevalence and constantly evolving patterns, with multidrug-resistant organisms (MDROs) creating new challenges every day. The most common mechanisms underlying AMR (i.e., genetic mutations, horizontal gene transfer, and selective pressure) contribute to the emergence and dissemination of new resistant strains. Therefore, mitigation strategies (e.g., antibiotic stewardship programs—ASPs—and infection prevention and control strategies—IPCs) emphasize the importance of responsible antimicrobial use and surveillance. A One Health approach (i.e., the interconnectedness of human, animal, and environmental health) highlights the necessity for interdisciplinary collaboration and holistic strategies in combating AMR. Advancements in novel therapeutics (e.g., alternative antimicrobial agents and vaccines) offer promising avenues in addressing AMR challenges. Policy interventions at the international and national levels also promote ASPs aiming to regulate antimicrobial use. Despite all of the observed progress, AMR remains a pressing concern, demanding sustained efforts to address emerging threats and promote antimicrobial sustainability. Future research must prioritize innovative approaches and address the complex socioecological dynamics underlying AMR. This manuscript is a comprehensive resource for researchers, policymakers, and healthcare professionals seeking to navigate the complex AMR landscape and develop effective strategies for its mitigation.
... At the various levels of organizational hierarchy, we see cases where adaptive variation has facilitated exaptations that have ultimately evolved into AMR mechanisms. We can tell transposases' primary function is in environmental adaptation as only a small percent carry AMR element; however, it does so highly efficiently, resulting in a large effect on AMR [60]. Promiscuous proteins in ancient bacteria were also able to bind and disrupt natural antimicrobials, an initial exaptation forming a portion of intrinsic resistance, and later gained broader functions. ...
Antimicrobial resistance (AMR) stands as a parallel pandemic, growing at an astonishing rate. Given the failing efficacy of traditional therapeutic approaches, it becomes imperative to grasp the urgency of this situation and frame robust solutions to impede the rising tide of antibiotic failures. In this chapter, we discuss the fundamentals of AMR biology, addressing the central role of evolution and natural selection in its development. Additionally, we analyze the impact of clinical pressures and their global ramifications on the spread of AMR. Thorough coverage of both conventional and advanced diagnostic methods for detecting AMR infections is reviewed. The latter sections of this chapter explore the new domain of systems biology, presenting its significance in understanding AMR mechanisms and identifying novel drug targets. Anticipated as a foundational guide, this chapter aims to set the stage for a profound, system-level exploration of AMR throughout the remainder of this book.
... Common bacterial infections have become the second leading cause of death worldwide, contributing to one in eight deaths globally. Antimicrobial resistance (AMR) in bacteria is recognized as a global problem affecting health and involves several key membrane proteins, including efflux proteins, pore proteins, and ribosomal protection proteins (Ramamurthy et al. 2022). Additionally, various enzymes located in the cell membrane also contribute to drug resistance. ...
... Jiang et al. (2017) provided evidence for the transfer of ARGs from actinobacteria to proteobacteria. Under the pressure of antibiotics, HGT fosters genomic diversity and rapid adaptation in bacteria (Ramamurthy et al., 2022). Antibiotics can amplify the dissemination of ARGs among gut bacterial communities, with profound and lasting impacts on microbial composition (Jutkina et al., 2016;Dhariwal et al., 2023). ...
Background
While antibiotics are commonly used to treat inflammatory bowel disease (IBD), their widespread application can disturb the gut microbiota and foster the emergence and spread of antibiotic resistance. However, the dynamic changes to the human gut microbiota and direction of resistance gene transmission under antibiotic effects have not been clearly elucidated.
Methods
Based on the Human Microbiome Project, a total of 90 fecal samples were collected from 30 IBD patients before, during and after antibiotic treatment. Through the analysis workflow of metagenomics, we described the dynamic process of changes in bacterial communities and resistance genes pre-treatment, during and post-treatment. We explored potential consistent relationships between gut microbiota and resistance genes, and established gene transmission networks among species before and after antibiotic use.
Results
Exposure to antibiotics can induce alterations in the composition of the gut microbiota in IBD patients, particularly a reduction in probiotics, which gradually recovers to a new steady state after cessation of antibiotics. Network analyses revealed intra-phylum transfers of resistance genes, predominantly between taxonomically close organisms. Specific resistance genes showed increased prevalence and inter-species mobility after antibiotic cessation.
Conclusion
This study demonstrates that antibiotics shape the gut resistome through selective enrichment and promotion of horizontal gene transfer. The findings provide insights into ecological processes governing resistance gene dynamics and dissemination upon antibiotic perturbation of the microbiota. Optimizing antibiotic usage may help limit unintended consequences like increased resistance in gut bacteria during IBD management.
... Various factors [72,73] are important for the expression of AMR genes, which may not be accurately reflected in culture and susceptibility testing conditions. Susceptibility testing may determine the in vitro susceptibility of the isolate at the time of sampling, but does not demonstrate the full AMR potential of the isolate. ...
Bovine respiratory disease (BRD) is the leading cause of mortality and antimicrobial drug (AMD) use in weaned dairy heifers. Limited information is available regarding antimicrobial resistance (AMR) in respiratory bacteria in this population. This study determined AMR gene presence in 326 respiratory isolates (Pasteurella multocida, Mannheimia haemolytica, and Histophilus somni) from weaned dairy heifers using whole genome sequencing. Concordance between AMR genotype and phenotype was determined. Twenty-six AMR genes for 8 broad classes of AMD were identified. The most prevalent, medically important AMD classes used in calf rearing, to which these genes predict AMR among study isolates were tetracycline (95%), aminoglycoside (94%), sulfonamide (94%), beta-lactam (77%), phenicol (50%), and macrolide (44%). The co-occurrence of AMR genes within an isolate was common; the largest cluster of gene co-occurrence encodes AMR to phenicol, macrolide, elfamycin, β-lactam (cephalosporin, penam cephamycin), aminoglycoside, tetracycline, and sulfonamide class AMD. Concordance between genotype and phenotype varied (Matthew’s Correlation Coefficient ranged from −0.57 to 1) by bacterial species, gene, and AMD tested, and was particularly poor for fluoroquinolones (no AMR genes detected) and ceftiofur (no phenotypic AMR classified while AMR genes present). These findings suggest a high genetic potential for AMR in weaned dairy heifers; preventing BRD and decreasing AMD reliance may be important in this population.
