In vitro resistance to the CSalphabeta-type antimicrobial peptide ASABF-alpha is conferred by overexpression of sigma factor sigB in Staphylococcus aureus

J Antimicrob Chemother. 2005 May;55(5):686-91. doi: 10.1093/jac/dki070. Epub 2005 Mar 10.

Abstract

Objectives: ASABF (Ascaris suum antibacterial factor) is a CSalphabeta-type antimicrobial peptide isolated from nematodes. ASABF-alpha, a member of ASABF, is particularly effective against the gram-positive pathogen Staphylococcus aureus. In this study, we investigated the role of sigB expression on ASABF-resistance in S. aureus.

Methods: Based on preliminary characterization of the ASABF-resistant strain, Mu50, we speculated that the alternative sigma factor sigB may regulate resistance against antimicrobial peptides. To test this hypothesis, the ASABF susceptibility was compared between NKSB (a sigB-knockout derivative of N315) and its sigB-overexpressing derivative. In addition, similar experiments were carried out for N315ex, a deletion mutant of N315 for SCCmec (Staphylococcus cassette chromosome mec) which contains essential genes for beta-lactam resistance.

Results: The sigB-overexpressing NKSB acquired an increased resistance to ASABF-alpha compared with the parent strain. The sigB-induced ASABF-alpha resistance was also observed in N315ex.

Conclusions: The overexpression of sigB confers resistance to the antimicrobial peptide, ASABF-alpha. SCCmec is not essential for this resistance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Drug Resistance, Bacterial*
  • Gene Expression Regulation, Bacterial
  • Helminth Proteins / pharmacology*
  • Microbial Sensitivity Tests
  • Penicillin-Binding Proteins
  • Peptides*
  • Sigma Factor / genetics
  • Sigma Factor / metabolism*
  • Staphylococcus aureus / drug effects*
  • Staphylococcus aureus / genetics
  • Staphylococcus aureus / metabolism
  • Up-Regulation

Substances

  • ASABF protein, Ascaris suum
  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Helminth Proteins
  • Penicillin-Binding Proteins
  • Peptides
  • SigB protein, Bacteria
  • Sigma Factor
  • mecA protein, Staphylococcus aureus