Antimicrobial Peptide Resistance Mechanism Contributes to Staphylococcus aureus Infection

J Infect Dis. 2018 Mar 13;217(7):1153-1159. doi: 10.1093/infdis/jiy024.

Abstract

Antimicrobial peptides (AMPs) constitute an important part of innate host defense. Possibly limiting the therapeutic potential of AMPs is the fact that bacteria have developed AMP resistance mechanisms during their co-evolution with humans. However, there is no direct evidence that AMP resistance per se is important during an infection. Here we show that the Staphylococcus aureus Pmt ABC transporter defends the bacteria from killing by important human AMPs and elimination by human neutrophils. By showing that Pmt contributes to virulence during skin infection in an AMP-dependent manner, we provide evidence that AMP resistance plays a key role in bacterial infection.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • ATP-Binding Cassette Transporters / genetics
  • ATP-Binding Cassette Transporters / metabolism*
  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • Antimicrobial Cationic Peptides / pharmacology*
  • Cathelicidins
  • Drug Resistance, Bacterial
  • Humans
  • Mice
  • Neutrophils / physiology*
  • Protein Conformation
  • Staphylococcal Skin Infections / drug therapy
  • Staphylococcal Skin Infections / microbiology
  • Staphylococcus aureus / drug effects*
  • Staphylococcus aureus / metabolism*

Substances

  • ATP-Binding Cassette Transporters
  • Anti-Bacterial Agents
  • Antimicrobial Cationic Peptides
  • Cathelicidins