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Science (New York, N.Y.)
05 01, 2020;368 (6490):

Antimicrobial peptides: Application informed by evolution.

Brian P Lazzaro, Michael Zasloff, Jens Rolff
Author Information
  1. Brian P Lazzaro: Department of Entomology, Cornell Institute of Host-Microbe Interactions and Disease, Cornell University, Ithaca, NY, USA. ORCID
  2. Michael Zasloff: MedStar Georgetown Transplant Institute, Georgetown University School of Medicine, Washington, DC, USA.
  3. Jens Rolff: Freie Universität Berlin, Evolutionary Biology, Institut für Biologie, Königin-Luise-Strasse 1-3, 14195 Berlin, Germany. jens.rolff@fu-berlin.de. ORCID
PMID: 32355003 DOI: 10.1126/science.aau5480

Abstract

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.

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Grants

  1. R01 AI141385/NIAID NIH HHS
  2. /European Research Council

MeSH Term

Animals
Anti-Bacterial Agents
Antimicrobial Cationic Peptides
Drosophila Proteins
Drug Resistance, Bacterial
Drug Synergism
Evolution, Molecular
Humans
Polymorphism, Genetic
Translational Research, Biomedical

Chemicals

Anti-Bacterial Agents
Antimicrobial Cationic Peptides
DptA protein, Drosophila
Drosophila Proteins
Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review
Article has an altmetric score of 113

Word Cloud

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