Antimicrobial peptides: Application informed by evolution
Antimicrobial peptides (AMPs) are essential components of immune defenses of multicellular organisms and are currently in development as anti-infective drugs. AMPs have been classically assumed to have broad-spectrum activity and simple kinetics, but recent evidence suggests an unexpected degree of...
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| Veröffentlicht in: | Science (American Association for the Advancement of Science) 2020-05, Vol.368 (6490) |
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| creator | Lazzaro, Brian P Zasloff, Michael Rolff, Jens |
| description | Antimicrobial peptides (AMPs) are essential components of immune defenses of multicellular organisms and are currently in development as anti-infective drugs. AMPs have been classically assumed to have broad-spectrum activity and simple kinetics, but recent evidence suggests an unexpected degree of specificity and a high capacity for synergies. Deeper evaluation of the molecular evolution and population genetics of AMP genes reveals more evidence for adaptive maintenance of polymorphism in AMP genes than has previously been appreciated, as well as adaptive loss of AMP activity. AMPs exhibit pharmacodynamic properties that reduce the evolution of resistance in target microbes, and AMPs may synergize with one another and with conventional antibiotics. Both of these properties make AMPs attractive for translational applications. However, if AMPs are to be used clinically, it is crucial to understand their natural biology in order to lessen the risk of collateral harm and avoid the crisis of resistance now facing conventional antibiotics. |
| doi_str_mv | 10.1126/science.aau5480 |
| format | Article |
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AMPs have been classically assumed to have broad-spectrum activity and simple kinetics, but recent evidence suggests an unexpected degree of specificity and a high capacity for synergies. Deeper evaluation of the molecular evolution and population genetics of AMP genes reveals more evidence for adaptive maintenance of polymorphism in AMP genes than has previously been appreciated, as well as adaptive loss of AMP activity. AMPs exhibit pharmacodynamic properties that reduce the evolution of resistance in target microbes, and AMPs may synergize with one another and with conventional antibiotics. Both of these properties make AMPs attractive for translational applications. However, if AMPs are to be used clinically, it is crucial to understand their natural biology in order to lessen the risk of collateral harm and avoid the crisis of resistance now facing conventional antibiotics.</description><identifier>ISSN: 0036-8075</identifier><identifier>EISSN: 1095-9203</identifier><identifier>DOI: 10.1126/science.aau5480</identifier><identifier>PMID: 32355003</identifier><language>eng</language><publisher>United States: The American Association for the Advancement of Science</publisher><subject>Acid resistance ; Amino acid sequence ; Amino acids ; Animal species ; Animals ; Anti-Bacterial Agents - pharmacology ; Antibiotic resistance ; Antibiotics ; Antifungal activity ; Antimicrobial agents ; Antimicrobial Cationic Peptides - chemistry ; Antimicrobial Cationic Peptides - genetics ; Antimicrobial Cationic Peptides - pharmacology ; Antimicrobial peptides ; Antiviral agents ; Bacteria ; Biodegradation ; Biological activity ; Biological evolution ; Biology ; Clinical trials ; Crises ; Drosophila Proteins - genetics ; Drosophila Proteins - pharmacology ; Drug development ; Drug resistance ; Drug Resistance, Bacterial ; Drug Synergism ; Eukaryotes ; Evidence ; Evolution ; Evolution, Molecular ; Evolutionary genetics ; Fungicides ; Gene duplication ; Gene families ; Gene polymorphism ; Genes ; Genetic diversity ; Genetics ; Humans ; Immunosuppressive agents ; Infections ; Low concentrations ; Molecular evolution ; Narcotics ; Peptides ; Pharmacodynamics ; Pharmacology ; Polymorphism ; Polymorphism, Genetic ; Population genetics ; Properties (attributes) ; Species ; Species diversity ; Synergism ; Translation ; Translational Medical Research</subject><ispartof>Science (American Association for the Advancement of Science), 2020-05, Vol.368 (6490)</ispartof><rights>Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. 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AMPs have been classically assumed to have broad-spectrum activity and simple kinetics, but recent evidence suggests an unexpected degree of specificity and a high capacity for synergies. Deeper evaluation of the molecular evolution and population genetics of AMP genes reveals more evidence for adaptive maintenance of polymorphism in AMP genes than has previously been appreciated, as well as adaptive loss of AMP activity. AMPs exhibit pharmacodynamic properties that reduce the evolution of resistance in target microbes, and AMPs may synergize with one another and with conventional antibiotics. Both of these properties make AMPs attractive for translational applications. However, if AMPs are to be used clinically, it is crucial to understand their natural biology in order to lessen the risk of collateral harm and avoid the crisis of resistance now facing conventional antibiotics.</description><subject>Acid resistance</subject><subject>Amino acid sequence</subject><subject>Amino acids</subject><subject>Animal species</subject><subject>Animals</subject><subject>Anti-Bacterial Agents - pharmacology</subject><subject>Antibiotic resistance</subject><subject>Antibiotics</subject><subject>Antifungal activity</subject><subject>Antimicrobial agents</subject><subject>Antimicrobial Cationic Peptides - chemistry</subject><subject>Antimicrobial Cationic Peptides - genetics</subject><subject>Antimicrobial Cationic Peptides - pharmacology</subject><subject>Antimicrobial peptides</subject><subject>Antiviral agents</subject><subject>Bacteria</subject><subject>Biodegradation</subject><subject>Biological activity</subject><subject>Biological evolution</subject><subject>Biology</subject><subject>Clinical trials</subject><subject>Crises</subject><subject>Drosophila Proteins - genetics</subject><subject>Drosophila Proteins - pharmacology</subject><subject>Drug development</subject><subject>Drug resistance</subject><subject>Drug Resistance, Bacterial</subject><subject>Drug Synergism</subject><subject>Eukaryotes</subject><subject>Evidence</subject><subject>Evolution</subject><subject>Evolution, Molecular</subject><subject>Evolutionary genetics</subject><subject>Fungicides</subject><subject>Gene duplication</subject><subject>Gene families</subject><subject>Gene polymorphism</subject><subject>Genes</subject><subject>Genetic diversity</subject><subject>Genetics</subject><subject>Humans</subject><subject>Immunosuppressive agents</subject><subject>Infections</subject><subject>Low concentrations</subject><subject>Molecular evolution</subject><subject>Narcotics</subject><subject>Peptides</subject><subject>Pharmacodynamics</subject><subject>Pharmacology</subject><subject>Polymorphism</subject><subject>Polymorphism, Genetic</subject><subject>Population genetics</subject><subject>Properties (attributes)</subject><subject>Species</subject><subject>Species diversity</subject><subject>Synergism</subject><subject>Translation</subject><subject>Translational Medical 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peptides: Application informed by evolution</title><author>Lazzaro, Brian P ; Zasloff, Michael ; Rolff, Jens</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c487t-cef01f264c3e249a2a2e2a060be39b321fdbac06752d2528117a9b5f310232ae3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Acid resistance</topic><topic>Amino acid sequence</topic><topic>Amino acids</topic><topic>Animal species</topic><topic>Animals</topic><topic>Anti-Bacterial Agents - pharmacology</topic><topic>Antibiotic resistance</topic><topic>Antibiotics</topic><topic>Antifungal activity</topic><topic>Antimicrobial agents</topic><topic>Antimicrobial Cationic Peptides - chemistry</topic><topic>Antimicrobial Cationic Peptides - genetics</topic><topic>Antimicrobial Cationic Peptides - pharmacology</topic><topic>Antimicrobial peptides</topic><topic>Antiviral 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AMPs have been classically assumed to have broad-spectrum activity and simple kinetics, but recent evidence suggests an unexpected degree of specificity and a high capacity for synergies. Deeper evaluation of the molecular evolution and population genetics of AMP genes reveals more evidence for adaptive maintenance of polymorphism in AMP genes than has previously been appreciated, as well as adaptive loss of AMP activity. AMPs exhibit pharmacodynamic properties that reduce the evolution of resistance in target microbes, and AMPs may synergize with one another and with conventional antibiotics. Both of these properties make AMPs attractive for translational applications. 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| subjects | Acid resistance Amino acid sequence Amino acids Animal species Animals Anti-Bacterial Agents - pharmacology Antibiotic resistance Antibiotics Antifungal activity Antimicrobial agents Antimicrobial Cationic Peptides - chemistry Antimicrobial Cationic Peptides - genetics Antimicrobial Cationic Peptides - pharmacology Antimicrobial peptides Antiviral agents Bacteria Biodegradation Biological activity Biological evolution Biology Clinical trials Crises Drosophila Proteins - genetics Drosophila Proteins - pharmacology Drug development Drug resistance Drug Resistance, Bacterial Drug Synergism Eukaryotes Evidence Evolution Evolution, Molecular Evolutionary genetics Fungicides Gene duplication Gene families Gene polymorphism Genes Genetic diversity Genetics Humans Immunosuppressive agents Infections Low concentrations Molecular evolution Narcotics Peptides Pharmacodynamics Pharmacology Polymorphism Polymorphism, Genetic Population genetics Properties (attributes) Species Species diversity Synergism Translation Translational Medical Research |
| title | Antimicrobial peptides: Application informed by evolution |
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