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      Comparing Selection on S. aureus between Antimicrobial Peptides and Common Antibiotics

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          Abstract

          With a diminishing number of effective antibiotics, there has been interest in developing antimicrobial peptides (AMPs) as drugs. However, any new drug faces potential bacterial resistance evolution. Here, we experimentally compare resistance evolution in Staphylococcus aureus selected by three AMPs (from mammals, amphibians and insects), a combination of two AMPs, and two antibiotics: the powerful last-resort vancomycin and the classic streptomycin. We find that resistance evolves readily against single AMPs and against streptomycin, with no detectable fitness cost. However the response to selection from our combination of AMPs led to extinction, in a fashion qualitatively similar to vancomycin. This is consistent with the hypothesis that simultaneous release of multiple AMPs during immune responses is a factor which constrains evolution of AMP resistant pathogens.

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          Antibiotics and antibiotic resistance genes in natural environments.

          Jose L. Muñoz Martinez (2008)
          The large majority of antibiotics currently used for treating infections and the antibiotic resistance genes acquired by human pathogens each have an environmental origin. Recent work indicates that the function of these elements in their environmental reservoirs may be very distinct from the "weapon-shield" role they play in clinical settings. Changes in natural ecosystems, including the release of large amounts of antimicrobials, might alter the population dynamics of microorganisms, including selection of resistance, with consequences for human health that are difficult to predict.
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            Genetic analysis of a high-level vancomycin-resistant isolate of Staphylococcus aureus.

            Linda Weigel, Don Clewell, Steven Gill … (2003)
            Vancomycin is usually reserved for treatment of serious infections, including those caused by multidrug-resistant Staphylococcus aureus. A clinical isolate of S. aureus with high-level resistance to vancomycin (minimal inhibitory concentration = 1024 microg/ml) was isolated in June 2002. This isolate harbored a 57.9-kilobase multiresistance conjugative plasmid within which Tn1546 (vanA) was integrated. Additional elements on the plasmid encoded resistance to trimethoprim (dfrA), beta-lactams (blaZ), aminoglycosides (aacA-aphD), and disinfectants (qacC). Genetic analyses suggest that the long-anticipated transfer of vancomycin resistance to a methicillin-resistant S. aureus occurred in vivo by interspecies transfer of Tn1546 from a co-isolate of Enterococcus faecalis.
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              Multifunctional cationic host defence peptides and their clinical applications.

              Amy Yeung, Shaan Gellatly, Robert E. W. Hancock (2011)
              With the rapid rise in the emergence of bacterial strains resistant to multiple classes of antimicrobial agents, there is an urgent need to develop novel antimicrobial therapies to combat these pathogens. Cationic host defence peptides (HDPs) and synthetic derivatives termed innate defence regulators (IDRs) represent a promising alternative approach in the treatment of microbial-related diseases. Cationic HDPs (also termed antimicrobial peptides) have emerged from their origins as nature's antibiotics and are widely distributed in organisms from insects to plants to mammals and non-mammalian vertebrates. Although their original and primary function was proposed to be direct antimicrobial activity against bacteria, fungi, parasites and/or viruses, cationic HDPs are becoming increasingly recognized as multifunctional mediators, with both antimicrobial activity and diverse immunomodulatory properties. Here we provide an overview of the antimicrobial and immunomodulatory activities of cationic HDPs, and discuss their potential application as beneficial therapeutics in overcoming infectious diseases.
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                Author and article information

                Contributors
                Herminia de Lencastre: Role: Editor
                Journal
                Journal ID (nlm-ta): PLoS One
                Journal ID (iso-abbrev): PLoS ONE
                Journal ID (publisher-id): plos
                Journal ID (pmc): plosone
                Title: PLoS ONE
                Publisher: Public Library of Science (San Francisco, USA )
                ISSN (Electronic): 1932-6203
                Publication date Collection: 2013
                Publication date (Electronic): 18 October 2013
                Volume: 8
                Issue: 10
                Electronic Location Identifier: e76521
                Affiliations
                [1 ]Animal & Plant Sciences, University of Sheffield, Western Bank, Sheffield, United Kingdom
                [2 ]Department of Entomology, Cornell University, Ithaca, New York, United States of America
                [3 ]School of Molecular Medical Sciences, University of Nottingham, Nottingham, United Kingdom
                [4 ]Faculty of Pharmacy, Gdansk University of Medicine, Gdansk, Poland
                [5 ]Institute of Biology, Free University Berlin, Berlin, Germany
                Rockefeller University, United States of America
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: AD JR. Performed the experiments: AD JP. Analyzed the data: AD. Contributed reagents/materials/analysis tools: WK. Wrote the paper: AD JR JP WK.

                Article
                Publisher ID: PONE-D-13-19838
                DOI: 10.1371/journal.pone.0076521
                PMC ID: 3799789
                PubMed ID: 24204634
                SO-VID: 18454bea-5615-407d-a560-d3de81af25df
                Copyright statement: Copyright @ 2013
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                Date received : 14 May 2013
                Date accepted : 1 September 2013
                Page count
                Pages: 5
                Funding
                Funding provided by ERCgrant Evoresin (grant number: 260986). AD was supported by a Biotechnology and Biological Sciences Research Council studentship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Subject: Research Article

                ScienceOpen disciplines: Uncategorized
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                ScienceOpen disciplines: Uncategorized

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