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      Co-Selection of Resistance to Antibiotics, Biocides and Heavy Metals, and Its Relevance to Foodborne Pathogens

      review-article
      * ,
      Antibiotics
      MDPI
      biocide, heavy metal, antimicrobial resistance, zoonoses

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          Abstract

          Concerns have been raised in recent years regarding co-selection for antibiotic resistance among bacteria exposed to biocides used as disinfectants, antiseptics and preservatives, and to heavy metals (particularly copper and zinc) used as growth promoters and therapeutic agents for some livestock species. There is indeed experimental and observational evidence that exposure to these non-antibiotic antimicrobial agents can induce or select for bacterial adaptations that result in decreased susceptibility to one or more antibiotics. This may occur via cellular mechanisms that are protective across multiple classes of antimicrobial agents or by selection of genetic determinants for resistance to non-antibiotic agents that are linked to genes for antibiotic resistance. There may also be relevant effects of these antimicrobial agents on bacterial community structure and via non-specific mechanisms such as mobilization of genetic elements or mutagenesis. Notably, some co-selective adaptations have adverse effects on fitness in the absence of a continued selective pressure. The present review examines the evidence for the significance of these phenomena, particularly in respect of bacterial zoonotic agents that commonly occur in livestock and that may be transmitted, directly or via the food chain, to human populations.

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          Most cited references175

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          Bacterial silver resistance: molecular biology and uses and misuses of silver compounds.

          Resistance to silver compounds as determined by bacterial plasmids and genes has been defined by molecular genetics. Silver resistance conferred by the Salmonella plasmid pMGH100 involves nine genes in three transcription units. A sensor/responder (SilRS) two-component transcriptional regulatory system governs synthesis of a periplasmic Ag(I)-binding protein (SilE) and two efflux pumps (a P-type ATPase (SilP) plus a three-protein chemiosmotic RND Ag(I)/H+ exchange system (SilCBA)). The same genes were identified on five of 19 additional IncH incompatibility class plasmids but thus far not on other plasmids. Of 70 random enteric isolates from a local hospital, isolates from catheters and other Ag-exposed sites, and total genomes of enteric bacteria, 10 have recognizable sil genes. The centrally located six genes are found and functional in the chromosome of Escherichia coli K-12, and also occur on the genome of E. coli O157:H7. The use of molecular epidemiological tools will establish the range and diversity of such resistance systems in clinical and non-clinical sources. Silver compounds are used widely as effective antimicrobial agents to combat pathogens (bacteria, viruses and eukaryotic microorganisms) in the clinic and for public health hygiene. Silver cations (Ag+) are microcidal at low concentrations and used to treat burns, wounds and ulcers. Ag is used to coat catheters to retard microbial biofilm development. Ag is used in hygiene products including face creams, "alternative medicine" health supplements, supermarket products for washing vegetables, and water filtration cartridges. Ag is generally without adverse effects for humans, and argyria (irreversible discoloration of the skin resulting from subepithelial silver deposits) is rare and mostly of cosmetic concern.
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            Alternative Antimicrobial Approach: Nano-Antimicrobial Materials

            Despite numerous existing potent antibiotics and other antimicrobial means, bacterial infections are still a major cause of morbidity and mortality. Moreover, the need to develop additional bactericidal means has significantly increased due to the growing concern regarding multidrug-resistant bacterial strains and biofilm associated infections. Consequently, attention has been especially devoted to new and emerging nanoparticle-based materials in the field of antimicrobial chemotherapy. The present review discusses the activities of nanoparticles as an antimicrobial means, their mode of action, nanoparticle effect on drug-resistant bacteria, and the risks attendant on their use as antibacterial agents. Factors contributing to nanoparticle performance in the clinical setting, their unique properties, and mechanism of action as antibacterial agents are discussed in detail.
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              Bacterial charity work leads to population-wide resistance

              Bacteria show remarkable adaptability in the face of antibiotic therapeutics. Resistance alleles in drug target-specific sites and general stress responses have been identified in individual endpoint isolates1–7. Less is known, however, about the population dynamics during the development of antibiotic-resistant strains. Here we follow a continuous culture of Escherichia coli facing increasing levels of antibiotic and show that the vast majority of isolates are less resistant than the population as a whole. We find that the few highly resistant mutants improve the survival of the population’s less resistant constituents, in part, by producing indole, a signaling molecule generated by actively growing, unstressed cells8. We show, through transcriptional profiling, that indole serves to turn on drug efflux pumps and oxidative stress protective mechanisms. The indole production comes at a fitness cost to the highly resistant isolates, and whole-genome sequencing reveals that this bacterial altruism is enabled by drug-resistance mutations unrelated to indole production. This work establishes a population-based resistance mechanism constituting a form of kin selection9 whereby a small number of resistant mutants can, at some cost to themselves, provide protection to other more vulnerable cells, enhancing the survival capacity of the overall population in stressful environments.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Antibiotics (Basel)
                Antibiotics (Basel)
                antibiotics
                Antibiotics
                MDPI
                2079-6382
                13 November 2015
                December 2015
                : 4
                : 4
                : 567-604
                Affiliations
                Department of Bacteriology and Food Safety, Animal and Plant Health Agency (Weybridge), Woodham Lane, New Haw, Addlestone, Surrey KT15 3NB, UK; E-Mail: rob.davies@ 123456apha.gsi.gov.uk
                Author notes
                [* ]Author to whom correspondence should be addressed; E-Mail: research@ 123456andy.wales ; Tel.: +44-2920-842-402.
                Article
                antibiotics-04-00567
                10.3390/antibiotics4040567
                4790313
                27025641
                b8101398-ca3d-40b1-979b-43438317832f
                © 2015 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 10 August 2015
                : 06 November 2015
                Categories
                Review

                biocide,heavy metal,antimicrobial resistance,zoonoses
                biocide, heavy metal, antimicrobial resistance, zoonoses

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