Coexpression of virulence and fosfomycin susceptibility in Listeria: molecular basis of an antimicrobial in vitro-in vivo paradox

Nat Med. 2006 May;12(5):515-7. doi: 10.1038/nm1396. Epub 2006 Apr 23.

Abstract

Discrepancies between resistance in vitro and therapeutic efficacy in vivo are generally attributed to failure of laboratory susceptibility tests to reflect an antibiotic's pharmacokinetic or pharmacodynamic properties. We show here that this phenomenon can result from differential in vitro-in vivo expression of bacterial determinants of antibiotic susceptibility. We found that an in vivo-induced virulence factor, Hpt, also mediates uptake of fosfomycin in Listeria monocytogenes. These bacteria therefore seem resistant to fosfomycin in vitro, although they are in fact susceptible to the antibiotic during infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents* / pharmacokinetics
  • Anti-Bacterial Agents* / therapeutic use
  • Drug Resistance, Bacterial*
  • Fosfomycin* / pharmacokinetics
  • Fosfomycin* / therapeutic use
  • Humans
  • In Vitro Techniques
  • Listeria monocytogenes* / pathogenicity
  • Listeria monocytogenes* / physiology
  • Listeriosis / drug therapy*
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / metabolism*
  • Microbial Sensitivity Tests
  • Peptide Termination Factors / genetics
  • Peptide Termination Factors / metabolism

Substances

  • Anti-Bacterial Agents
  • Hpt permease, Listeria monocytogenes
  • Membrane Transport Proteins
  • Peptide Termination Factors
  • Fosfomycin