A liaF codon deletion abolishes daptomycin bactericidal activity against vancomycin-resistant Enterococcus faecalis

Antimicrob Agents Chemother. 2013 Jun;57(6):2831-3. doi: 10.1128/AAC.00021-13. Epub 2013 Mar 18.

Abstract

The genetic bases for antibiotic tolerance are obscure. Daptomycin (DAP) is a lipopeptide antibiotic with bactericidal activity against enterococci. Using time-kill assays, we provide evidence for the first time that a deletion of isoleucine in position 177 of LiaF, a member of the three-component regulatory system LiaFSR involved in the cell envelope response to antimicrobials, is directly responsible for a DAP-tolerant phenotype and is likely to negatively affect response to DAP therapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Bacterial Proteins / genetics*
  • Cell Wall / drug effects
  • Codon / genetics*
  • Daptomycin / pharmacology*
  • Drug Resistance, Bacterial / genetics*
  • Enterococcus faecium / drug effects*
  • Humans
  • Microbial Sensitivity Tests / standards
  • Sequence Analysis, DNA
  • Sequence Deletion / genetics*
  • Stem Cells
  • Vancomycin / pharmacology
  • Vancomycin Resistance

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Codon
  • Vancomycin
  • Daptomycin