Therapeutic antimicrobial peptides may compromise natural immunity
Antimicrobial peptides (AMPs) have been proposed as a promising new class of antimicrobials despite warnings that therapeutic use could drive the evolution of pathogens resistant to our own immunity peptides. Using experimental evolution, we demonstrate that Staphylococcus aureus rapidly evolved res...
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| Veröffentlicht in: | Biology letters (2005) 2012-06, Vol.8 (3), p.416-418 |
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| creator | Habets, Michelle G. J. L. Brockhurst, Michael A. |
| description | Antimicrobial peptides (AMPs) have been proposed as a promising new class of antimicrobials despite warnings that therapeutic use could drive the evolution of pathogens resistant to our own immunity peptides. Using experimental evolution, we demonstrate that Staphylococcus aureus rapidly evolved resistance to pexiganan, a drug-candidate for diabetic leg ulcer infections. Evolved resistance was costly in terms of impaired growth rate, but costs-of-resistance were completely ameliorated by compensatory adaptation. Crucially, we show that, in some populations, experimentally evolved resistance to pexiganan provided S. aureus with cross-resistance to human-neutrophil-defensin-1, a key component of the innate immune response to infection. This unintended consequence of therapeutic use could drastically undermine our innate immune system's ability to control and clear microbial infections. Our results therefore highlight grave potential risks of AMP therapies, with implications for their development. |
| doi_str_mv | 10.1098/rsbl.2011.1203 |
| format | Article |
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J. L.</creatorcontrib><creatorcontrib>Brockhurst, Michael A.</creatorcontrib><title>Therapeutic antimicrobial peptides may compromise natural immunity</title><title>Biology letters (2005)</title><addtitle>Biol. Lett</addtitle><addtitle>Biol. Lett</addtitle><description>Antimicrobial peptides (AMPs) have been proposed as a promising new class of antimicrobials despite warnings that therapeutic use could drive the evolution of pathogens resistant to our own immunity peptides. Using experimental evolution, we demonstrate that Staphylococcus aureus rapidly evolved resistance to pexiganan, a drug-candidate for diabetic leg ulcer infections. Evolved resistance was costly in terms of impaired growth rate, but costs-of-resistance were completely ameliorated by compensatory adaptation. Crucially, we show that, in some populations, experimentally evolved resistance to pexiganan provided S. aureus with cross-resistance to human-neutrophil-defensin-1, a key component of the innate immune response to infection. This unintended consequence of therapeutic use could drastically undermine our innate immune system's ability to control and clear microbial infections. Our results therefore highlight grave potential risks of AMP therapies, with implications for their development.</description><subject>alpha-Defensins - pharmacology</subject><subject>Anti-Infective Agents - pharmacology</subject><subject>Antibiotic Resistance</subject><subject>Antimicrobial Cationic Peptides - pharmacology</subject><subject>Antimicrobial Peptide</subject><subject>Biological Evolution</subject><subject>Compensatory Adaptation</subject><subject>Cost-Of-Resistance</subject><subject>Drug Resistance, Bacterial</subject><subject>Drug Resistance, Multiple</subject><subject>Evolutionary Biology</subject><subject>Experimental Evolution</subject><subject>Humans</subject><subject>Immunity, Innate</subject><subject>Innate Immunity</subject><subject>Selection, Genetic</subject><subject>Staphylococcal Infections - immunology</subject><subject>Staphylococcal Infections - microbiology</subject><subject>Staphylococcus aureus</subject><subject>Staphylococcus aureus - drug effects</subject><subject>Staphylococcus aureus - genetics</subject><issn>1744-9561</issn><issn>1744-957X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkUmP1DAQhSMEYha4ckQ5cknjshPbuSAxAwNILSFBg7hZjlNhPCRxsJ0R4dfjVoYWi1hOtlWfX72ql2UPgGyA1PKxD02_oQRgA5SwW9kxiLIs6kp8uH24czjKTkK4IoQJQaq72RGlVNRQsePsbHeJXk84R2tyPUY7WONdY3WfTzhF22LIB73kxg2Td4MNmI86zj7V7TDMo43LvexOp_uA92_O0-zdxfPd-cti-_rFq_On28JwKmPRkFK2HWla1tFSGi27Bhi2WJq2qXkHNUKJHe2MkLVmLerWmK4hWnOoK2MIO82erLrT3AzYGhxjsqEmbwftF-W0VT9XRnupPrprxRgXgrMk8OhGwLvPM4ao0jwG-16P6OagoKqAA-NA_o0SSmQpSiH_AwWWuteSJnSzomnFIXjsDuaBqH2cah-n2sep9nGmDw9_HPmAf88vAWwFvFvS7p2xGBd15WY_puefZfXffr15e7a9lpYpIhkQAYJy9dVOq4pUNoQZFftF9PcexdrDhohfDs61_6S4YKJS72Wp2E5smUwun7FvrNbfXg</recordid><startdate>20120623</startdate><enddate>20120623</enddate><creator>Habets, Michelle G. 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J. L.</au><au>Brockhurst, Michael A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Therapeutic antimicrobial peptides may compromise natural immunity</atitle><jtitle>Biology letters (2005)</jtitle><stitle>Biol. Lett</stitle><addtitle>Biol. Lett</addtitle><date>2012-06-23</date><risdate>2012</risdate><volume>8</volume><issue>3</issue><spage>416</spage><epage>418</epage><pages>416-418</pages><issn>1744-9561</issn><eissn>1744-957X</eissn><abstract>Antimicrobial peptides (AMPs) have been proposed as a promising new class of antimicrobials despite warnings that therapeutic use could drive the evolution of pathogens resistant to our own immunity peptides. Using experimental evolution, we demonstrate that Staphylococcus aureus rapidly evolved resistance to pexiganan, a drug-candidate for diabetic leg ulcer infections. 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| ispartof | Biology letters (2005), 2012-06, Vol.8 (3), p.416-418 |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | alpha-Defensins - pharmacology Anti-Infective Agents - pharmacology Antibiotic Resistance Antimicrobial Cationic Peptides - pharmacology Antimicrobial Peptide Biological Evolution Compensatory Adaptation Cost-Of-Resistance Drug Resistance, Bacterial Drug Resistance, Multiple Evolutionary Biology Experimental Evolution Humans Immunity, Innate Innate Immunity Selection, Genetic Staphylococcal Infections - immunology Staphylococcal Infections - microbiology Staphylococcus aureus Staphylococcus aureus - drug effects Staphylococcus aureus - genetics |
| title | Therapeutic antimicrobial peptides may compromise natural immunity |
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