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

Nature Medicine volume 12, pages 515–517 (2006)Cite this article

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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Figure 1: L.monocytogenes is resistant in vitro but susceptible intracellularly and in vivo to fosfomycin (Supplementary Methods online).
Figure 2: Intracellular counterselection of L. monocytogenes FMR mutants in J774 macrophages (Supplementary Methods online).

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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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Author notes

  1. Martin Wagner

    Present address: University of Veterinary Medicine, 1210, Vienna, Austria

  2. Mariela Scortti, Lizeth Lacharme-Lora and Martin Wagner: These authors contributed equally to this work.

Authors and Affiliations

  1. Bacterial Molecular Pathogenesis Group, Faculty of Medical and Veterinary Sciences, University of Bristol, Langford, BS40 5DU, UK

    Mariela Scortti, Lizeth Lacharme-Lora, Patrizia Losito & José A Vázquez-Boland

  2. Grupo de Patogénesis Molecular Bacteriana, Facultad de Veterinaria, Universidad Complutense de Madrid, Madrid, 28040, Spain

    Mariela Scortti, Martin Wagner, Isabel Chico-Calero & José A Vázquez-Boland

  3. Grupo de Patogénesis Molecular y Genómica Bacteriana, Facultad de Veterinaria, Universidad de León, León, 24071, Spain

    Mariela Scortti, Lizeth Lacharme-Lora & José A Vázquez-Boland

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  1. Mariela Scortti
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Correspondence to José A Vázquez-Boland.

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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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