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Confocal laser scanning microscopy images of Salmonella Typhimurium ATCC 14028 biofilms grown in the presence of different ZnCl2 concentrations (0:a, 250:b or 500 μ mol l−1:c). Biofilms were stained with FilmTracerTM FM® 1–43.
Source publication
Aims:
Biofilm formation is important for the persistence of bacteria in hostile environments. Bacteria in a biofilm are usually more resistant to antibiotics and disinfectants than planktonic bacteria. Our laboratory previously reported that low concentrations of zinc inhibit biofilm formation of Actinobacillus pleuropneumoniae. The aim of this st...
Contexts in source publication
Context 1
... effect of zinc confirmed by CLSM To confirm the inhibitory effect of zinc on biofilm formation, we used CLSM and fluorescent staining to visualize the zinc-treated and control biofilms. Biofilm formation by Salm. Typhimurium in the presence of ZnCl 2 is shown as an example (Fig. 4). As observed with the microtitre plate assay and crystal violet staining, Salm. Typhimurium formed markedly less biofilm than the control when grown in the presence of 250 and 500 l mol l À1 of ZnCl 2 (Fig. ...
Context 2
... visualize the zinc-treated and control biofilms. Biofilm formation by Salm. Typhimurium in the presence of ZnCl 2 is shown as an example (Fig. 4). As observed with the microtitre plate assay and crystal violet staining, Salm. Typhimurium formed markedly less biofilm than the control when grown in the presence of 250 and 500 l mol l À1 of ZnCl 2 (Fig. ...
Citations
... Owing to the urgent need for alternative antimicrobial options, the application of combined therapy has attracted the attention of many scientists and clinicians as an effective strategy to overcome infections associated with biofilms. This approach might be addressed via the combination between conventional antibiotics and zinc as one of the trace elements which is essential for many vital processes [6] and with previously demonstrated antibiofilm efficacy [8]. Consequently, the current study aimed to explore the antimicrobial interaction pattern between zinc sulfate and different classes of antibiotics including cephalosporins, fluoroquinolones, aminoglycosides, and carbapenems against biofilm-forming K. pneumoniae. ...
... Zinc could react with the constituents of the bacterial biofilm such as poly-n-acetylglucosamine (PGA). On the other side, the ability of zinc to inhibit the bacterial biofilms of other microorganisms that lack PGA in their biofilms indicated that it is not the only inhibitory mechanism [8]. Another study suggested that the chelation between zinc and extracellular DNA as a component of the biofilm matrix could affect biofilm stability [22]. ...
Background
Klebsiella pneumoniae is a significant healthcare-associated pathogen. We investigated the antimicrobial interaction pattern between zinc sulfate and antibiotics against K. pneumoniae biofilm on the phenotypic and genotypic levels.
Methods
Determining the minimum biofilm inhibitory concentrations and the transcriptomic profile of K. pneumoniae biofilm formation genes post-treatment were carried out to evaluate the effect on the phenotypic and genotypic levels, respectively.
Results
Zinc enhanced the antibiofilm potentials of cephalosporins, aminoglycosides, and ertapenem, whereas it antagonizes the effectiveness of fluoroquinolones and meropenem on the phenotypic level. On the molecular level, zinc enhanced the anti-biofilm efficacies of cephalosporins (cefotaxime, ceftriaxone, ceftazidime, cefpirome, and cefepime) via down-regulating the expression of biofilm-related genes by 18-, 38-, 5-, 77- and 2-folds, respectively. Zinc in combination with aminoglycosides (kanamycin, gentamicin, and amikacin) reduced the expression of biofilm-related genes by 40-, 2602- and 20-folds, respectively, and by 2-folds in combination with ertapenem. However, a reduction in the down-regulatory potentials of fluoroquinolones was recorded following combination with zinc by 2-, 2-, 15- and 14-folds, respectively, and an up-regulation in the expression levels of the tested genes by 2-folds in the case of zinc/meropenem combination.
Conclusions
Results revealed variable interaction patterns between different antibiotics in combination with zinc. Current findings also shed light on the antibiofilm potentials of zinc/antibiotics combinations especially when combining zinc with fluoroquinolones or meropenem to avoid their antagonistic effects.
... In vitro studies demonstrated that various bacterial species are inhibited by zinc. This also explains the ability of zinc to prevent biofilm formation [81]. However, methicillin resistance, among other strains, is evident and zinc's capacity to inhibit biofilms is limited [24,69]. ...
... Several published studies claim antimicrobial effects of metal ions [39,[77][78][79][80][81][82]. Very few of these claims hold up against biofilm forming microbial strains. ...
In healthy skin, vectorial ion transport gives rise to a transepithelial potential which directly impacts many physiological aspects of skin function. A wound is a physical defect that breaches the epithelial barrier and changes the electrochemical environment of skin. Electroceutical dressings are devices that manipulate the electrochemical environment, host as well as microbial, of a wound. In this review, electroceuticals are organized into three mechanistic classes: ionic, wireless, and battery powered. All three classes of electroceutical dressing show encouraging effects on infection management and wound healing with evidence of favorable impact on keratinocyte migration and disruption of wound biofilm infection. This foundation sets the stage for further mechanistic as well as interventional studies. Successful conduct of such studies will determine the best dosage, timing, and class of stimulus necessary to maximize therapeutic efficacy.
... One of the most efficient ions against bacterial biofilm is zinc (Zn) [74,75]. Zn is a multifunctional therapeutic ion. ...
... Zn is a multifunctional therapeutic ion. Zn can stimulate bone formation because it is a cofactor in many enzymes and is involved in DNA replication [74]. Zn can also leak from the BG, causing oxidative stress in the intracellular medium or damage to cell membranes [76]. ...
One of the major clinical issues during the implantation procedure is the bacterial infections linked to biofilms. Due to their tissue localization and the type of bacteria involved, bacterial infections at implant sites are usually difficult to treat, which increases patient morbidity and even mortality. The difficulty of treating biofilm-associated infections and the emergence of multidrug-resistant bacteria are further challenges for the scientific community to develop novel biomaterials with excellent biocompatibility and antibacterial properties. Given their ability to stimulate bone formation and have antibacterial properties, metal ion-doped bioactive glasses (BGs) have received considerable research. This mini review aims to be successful in presenting the developments made about the role of biocide metal ions incorporated into BGs against the development of bacterial biofilms and the spread of nosocomial diseases.
... Zinc can be bound to a ferric uptake regulator and affect iron homeostasis. Zinc also inhibits the cyclic diguanylate phosphodiesterase pathway which plays a role in biofilm regulation so that zinc will interfere with the biofilm formation process (Wu et al, 2013). ...
Background: Klebsiella pneumoniae is a Gram-negative bacterium that form biofilm and causes various infections. Biofilms have important role in resistance to antibiotics. Alternative agents that can inhibit biofilms formation with minimal side effects is required. This study show effects of vitamin C and zinc to inhibit Klebsiella pneumoniae biofilms formation. Method: This experiment used clinically stored Klebsiella pneumoniae isolates using controls. Isolates other than control are exposed with vitamin C and zinc oral preparations with various doses invitro then Optical Density and percentage reduction in biofilm is calculated and compared. Results: Vitamin C and zinc had invitro-inhibiting effect on biofilms formation of Klebsiella pneumoniae at all doses. The differences in decrease of Optical Density biofilm from the doses used after statistical testing was significant (P < 0.05). The smallest Optical Density and the largest percentage of Optical Density reduction of biofilms is found in vitamin C 1000 mg and zinc 50 mg. Conclusion: There are differences in inhibition of biofilm formation Klebsiella pneumoniae in the administration of vitamin C and zinc, with higher dose of vitamin C and zinc, the inhibition of biofilms formation is greater.
... With the corrosion of Zn or Mg, the increasing amount of OH À ions contributes to the growing alkalinity of the solution and thus decreases bacteria viability, as it is believed that most bacteria can only survive in a pH range of 6-8.88 However, Zn itself demonstrates antibacterial properties against different pathogens.89 According to the Pourbaix diagram, in an environment of pH <7.4, ...
In vitro cytotoxicity assessment is indispensable in developing new biodegradable implant materials. Zn, which demonstrates an ideal corrosion rate between Mg‐ and Fe‐based alloys, has been reported to have excellent in vivo biocompatibility. Therefore, modifications aimed at improving Zn's mechanical properties should not degrade its biological response. As sufficient strength, ductility and corrosion behavior required of load‐bearing implants has been obtained in plastically deformed Zn‐3Ag‐0.5Mg, the effect of simultaneous Ag and Mg additions on in vitro cytocompatibility and antibacterial properties was studied, in relation to Zn and Zn‐3Ag. Direct cell culture on samples and indirect extract‐based tests showed almost no significant differences between the tested Zn‐based materials. The diluted extracts of Zn, Zn‐3Ag, and Zn‐3Ag‐0.5Mg showed no cytotoxicity toward MG‐63 cells at a concentration of ≤12.5%. The cytotoxic effect was observed only at high Zn2+ ion concentrations and when in direct contact with metallic samples. The highest LD50 (lethal dose killing 50% of cells) of 13.4 mg/L of Zn2+ ions were determined for the Zn‐3Ag‐0.5Mg. Similar antibacterial activity against Escherichia coli and Staphylococcus aureus was observed for Zn and Zn alloys, so the effect is attributed mainly to the released Zn2+ ions exhibiting bactericidal properties. Most importantly, our experiments indicated the limitations of water‐soluble tetrazolium salt‐based cytotoxicity assays for direct tests on Zn‐based materials. The discrepancies between the WST‐8 assay and SEM observations are attributed to the interference of Zn2+ ions with tetrazolium salt, therefore favoring its transformation into formazan, giving false cell viability quantitative results.
... 40 Zinc ions were shown to interfere with P. aeruginosa biofilm formation and inhibit planktonic growth of the bacterium. 41 Gallium is attracting attention as an antimicrobial agent, 42 with forms of gallium-containing drugs currently being discussed with regard to P. aeruginosa treatment, such as gallium complexes with organic molecules, such as acetate 43 or desferrioxamin. 44 Co-crystallization of silver with PF in our work reflected MIC values between those of PF and AgNO 3 individually. ...
Here, we exploit our mechanochemical synthesis for co-crystallization of an organic antiseptic, proflavine, with metal-based antimicrobials (silver, copper, zinc, and gallium). Our previous studies have looked for general antimicrobial activity for the co-crystals: proflavine·AgNO3, proflavine·CuCl, ZnCl3[Proflavinium], [Proflavinium]2[ZnCl4]·H2O, and [Proflavinium]3[Ga(oxalate)3]·4H2O. Here, we explore and compare more precisely the bacteriostatic (minimal inhibitory concentrations) and antibiofilm (prevention of cell attachment and propagation) activities of the co-crystals. For this, we choose three prominent "ESKAPE" bacterial pathogens of Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus aureus. The antimicrobial behavior of the co-crystals was compared to that of the separate components of the polycrystalline samples to ascertain whether the proflavine-metal complex association in the solid state provided effective antimicrobial performance. We were particularly interested to see if the co-crystals were effective in preventing bacteria from initiating and propagating the biofilm mode of growth, as this growth form provides high antimicrobial resistance properties. We found that for the planktonic lifestyle of growth of the three bacterial strains, different co-crystal formulations gave selectivity for best performance. For the biofilm state of growth, we see that the silver proflavine co-crystal has the best overall antibiofilm activity against all three organisms. However, other proflavine-metal co-crystals also show practical antimicrobial efficacy against E. coli and S. aureus. While not all proflavine-metal co-crystals demonstrated enhanced antimicrobial efficacy over their constituents alone, all possessed acceptable antimicrobial properties while trapped in the co-crystal form. We also demonstrate that the metal-proflavine crystals retain antimicrobial activity in storage. This work defines that co-crystallization of metal compounds and organic antimicrobials has a potential role in the quest for antimicrobials/antiseptics in the defense against bacteria in our antimicrobial resistance era.
... and, therefore, pathogenicity. This has been shown in S. pneumoniae, S. pyogenes, S. mutans, and S. suis [28,106,111,112]. The Zn efflux systems in Streptococci are, therefore, necessary to overcome Zn toxicity by ridding the cell of extra Zn and contributing to Streptococcal infections [16,30,58,96,[113][114][115]. ...
Streptococcus spp. are an important genus of Gram-positive bacteria, many of which are opportunistic pathogens that are capable of causing invasive disease in a wide range of populations. Metals, especially transition metal ions, are an essential nutrient for all organisms. Therefore, to survive across dynamic host environments, Streptococci have evolved complex systems to withstand metal stress and maintain metal homeostasis, especially during colonization and infection. There are many different types of transport systems that are used by bacteria to import or export metals that can be highly specific or promiscuous. Focusing on the most well studied transition metals of zinc, manganese, iron, nickel, and copper, this review aims to summarize the current knowledge of metal homeostasis in pathogenic Streptococci, and their role in virulence.
... When treated with an equivalent amount of free Zn 2+ (1.06 ppm, 16.2 μM) on days 1 and 2, the wound area increased in size similar to the control group (Figure 3, S19b), as expected since this concentration of Zn 2+ is known to be too low to prevent the formation of biofilms by most pathogenic bacteria. 60 With phanorod and phanorod-Zn treatment (day 0: reagent applied and incubated for 30 min, after wound inoculation, and irradiated for 15 min; day 1: irradiated again for 15 min), the wound temperature rapidly increased to ∼55°C in 2−3 min during laser irradiation (Figures 3a and S18). With phanorod and phanorod-Zn treatment, wound size did not increase and instead decreased markedly over the next several days; by day 4, the wound area with treatment was <20% of the area of an untreated wound. ...
Infections caused by drug-resistant bacteria, particularly Gram-negative organisms, are increasingly difficult to treat using antibiotics. A potential alternative is "phage therapy", in which phages infect and lyse the bacterial host. However, phage therapy poses serious drawbacks and safety concerns, such as the risk of genetic transduction of antibiotic resistance genes, inconsistent pharmacokinetics, and unknown evolutionary potential. In contrast, metallic nanoparticles possess precise, tunable properties, including efficient conversion of electronic excitation into heat. In this work, we demonstrate that engineered phage-nanomaterial conjugates that target the Gram-negative pathogen Pseudomonas aeruginosa are highly effective as a treatment of infected wounds in mice. Photothermal heating, performed as a single treatment (15 min) or as two treatments on consecutive days, rapidly reduced the bacterial load and released Zn2+ to promote wound healing. The phage-nanomaterial treatment was significantly more effective than systemic standard-of-care antibiotics, with a >10× greater reduction in bacterial load and ∼3× faster healing as measured by wound size reduction when compared to fluoroquinolone treatment. Notably, the phage-nanomaterial was also effective against a P. aeruginosa strain resistant to polymyxins, a last-line antibiotic therapy. Unlike these antibiotics, the phage-nanomaterial showed no detectable toxicity or systemic effects in mice, consistent with the short duration and localized nature of phage-nanomaterial treatment. Our results demonstrate that phage therapy controlled by inorganic nanomaterials can be a safe and effective antimicrobial strategy in vivo.
... Subsequently, the untreated wounds decreased slowly in size, reaching the original wound size on day 8, but were not closed by day 10. When treated with an equivalent amount of free Zn 2+ (1.06 ppm) on day 1 and 2, the wound area increased in size similar to the control group ( Figure 3, S19b), as expected since this concentration of Zn 2+ is known to be too low to prevent the formation of biofilms by most pathogenic bacteria 56 . ...
Infections caused by drug-resistant bacteria, particularly gram-negative organisms, are increasingly difficult to treat using antibiotics. A potential alternative is phage therapy, in which phages infect and lyse the bacterial host. However, phage therapy poses serious drawbacks and safety concerns, such as the risk of genetic transduction of antibiotic resistance genes, inconsistent pharmacokinetics, and unknown evolutionary potential. In contrast, metallic nanoparticles possess precise, tunable properties, including efficient conversion of electronic excitation into heat. In this work, we demonstrate that engineered phage-nanomaterial conjugates that target the gram-negative pathogen P. aeruginosa, are highly effective as a treatment of infected wounds in mice. Photothermal heating, performed as a single treatment (15 min) or as two treatments on consecutive days, rapidly reduced the bacterial load and released Zn2+ to promote wound healing. The phage-nanomaterial treatment was significantly more effective than systemic fluoroquinolone antibiotics in reducing both bacterial load and wound size, and was notably effective against a P. aeruginosa strain resistant to polymyxins, a last-line antibiotic therapy. Unlike these antibiotics, the phage-nanomaterial showed no detectable toxicity or systemic effects in mice, consistent with the short duration and localized nature of phage-nanomaterial treatment. Our results demonstrate that phage therapy controlled by inorganic nanomaterials can be a safe and effective antimicrobial strategy in vivo.
... Following the golden rule that "the dose makes the poison" (Paracelsus), excessive Zn levels may also be toxic for pathogenic bacteria. Particularly, Zn 2+ may exert an inhibitory effect by interfering with Mn 2+ metabolism [9], development of oxidative stress [10], and inhibition of biofilm formation [11]. ...
The objective of the present study was to review the existing data on the association between Zn status and characteristics of gut microbiota in various organisms and the potential role of Zn-induced microbiota in modulating systemic effects. The existing data demonstrate a tight relationship between Zn metabolism and gut microbiota as demonstrated in Zn deficiency, supplementation, and toxicity studies. Generally, Zn was found to be a significant factor for gut bacteria biodiversity. The effects of physiological and nutritional Zn doses also result in improved gut wall integrity, thus contributing to reduced translocation of bacteria and gut microbiome metabolites into the systemic circulation. In contrast, Zn overexposure induced substantial alterations in gut microbiota. In parallel with intestinal effects, systemic effects of Zn-induced gut microbiota modulation may include systemic inflammation and acute pancreatitis, autism spectrum disorder and attention deficit hyperactivity disorder, as well as fetal alcohol syndrome and obesity. In view of both Zn and gut microbiota, as well as their interaction in the regulation of the physiological functions of the host organism, addressing these targets through the use of Zn-enriched probiotics may be considered an effective strategy for health management.
