Coexpression of virulence and fosfomycin susceptibility in Listeria: molecular basis of an antimicrobial in vitro-in vivo paradox.
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.
Scortti
Mariela
M
Bacterial Molecular Pathogenesis Group, Faculty of Medical and Veterinary Sciences, University of Bristol, Langford BS40 5DU, UK.
Lacharme-Lora
Lizeth
L
Wagner
Martin
M
Chico-Calero
Isabel
I
Losito
Patrizia
P
Vázquez-Boland
José A
JA
D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D024881:Drug Resistance, Bacterial; D005578:Fosfomycin / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D066298:In Vitro Techniques; D008089:Listeria monocytogenes / Q000472:pathogenicity / Q000502:physiology; D008088:Listeriosis / Q000188:drug therapy*; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D008826:Microbial Sensitivity Tests; D010454:Peptide Termination Factors / Q000235:genetics / Q000378:metabolism
D000900:Anti-Bacterial Agents; C451411:Hpt permease, Listeria monocytogenes; D026901:Membrane Transport Proteins; D010454:Peptide Termination Factors; D005578:Fosfomycin