Antimicrobials, stress and mutagenesis

PLoS Pathog. 2014 Oct 9;10(10):e1004445. doi: 10.1371/journal.ppat.1004445. eCollection 2014 Oct.

Abstract

Cationic antimicrobial peptides are ancient and ubiquitous immune effectors that multicellular organisms use to kill and police microbes whereas antibiotics are mostly employed by microorganisms. As antimicrobial peptides (AMPs) mostly target the cell wall, a microbial 'Achilles heel', it has been proposed that bacterial resistance evolution is very unlikely and hence AMPs are ancient 'weapons' of multicellular organisms. Here we provide a new hypothesis to explain the widespread distribution of AMPs amongst multicellular organism. Studying five antimicrobial peptides from vertebrates and insects, we show, using a classic Luria-Delbrück fluctuation assay, that cationic antimicrobial peptides (AMPs) do not increase bacterial mutation rates. Moreover, using rtPCR and disc diffusion assays we find that AMPs do not elicit SOS or rpoS bacterial stress pathways. This is in contrast to the main classes of antibiotics that elevate mutagenesis via eliciting the SOS and rpoS pathways. The notion of the 'Achilles heel' has been challenged by experimental selection for AMP-resistance, but our findings offer a new perspective on the evolutionary success of AMPs. Employing AMPs seems advantageous for multicellular organisms, as it does not fuel the adaptation of bacteria to their immune defenses. This has important consequences for our understanding of host-microbe interactions, the evolution of innate immune defenses, and also sheds new light on antimicrobial resistance evolution and the use of AMPs as drugs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Infective Agents / immunology
  • Anti-Infective Agents / pharmacology*
  • Antimicrobial Cationic Peptides / immunology
  • Antimicrobial Cationic Peptides / pharmacology*
  • Bacteria / immunology
  • Immunity, Innate / immunology
  • Mutagenesis / immunology*
  • Vertebrates / immunology*

Substances

  • Anti-Infective Agents
  • Antimicrobial Cationic Peptides

Grants and funding

ARR and JR were supported SFB 973 (Deutsche Forschungsgemeinschaft), project C%) and OM and JR by European Research Council grant 260986 to JR. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.