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.
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Acknowledgements
We thank B. González-Zorn for advice on mouse experiments, S. Novella for assistance with the isolate collection, the personnel of the animal facility of the Universidad Complutense of Madrid (UCM) for animal care, and D. Lewis and C. Helps for reading the manuscript. We also thank F. Baquero for discussions. Mouse tests were performed when the group was based at UCM according to current regulations on animal experimentation. This work was supported by the Spanish Ministry for Science and Technology (grant BMC2000-0553), the European Commission (contract QLG2-CT-1999-00932), and in the UK by the Wellcome Trust (program grant 074020). M.W. was supported by a Schrödinger visiting fellowship from the Austrian Research Fund (J-1694).
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Scortti, M., Lacharme-Lora, L., Wagner, M. et al. Coexpression of virulence and fosfomycin susceptibility in Listeria: molecular basis of an antimicrobial in vitro–in vivo paradox. Nat Med 12, 515–517 (2006). https://doi.org/10.1038/nm1396
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DOI: https://doi.org/10.1038/nm1396
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