The MprF protein is required for lysinylation of phospholipids in listerial membranes and confers resistance to cationic antimicrobial peptides (CAMPs) on Listeria monocytogenes

Authors

  • Kathrin Thedieck,

    1. Helmholtz Centre for Infection Research, Division of Cell and Immune Biology, Cellular Proteomics Group, Inhoffenstraße 7, D-38124 Braunschweig, Germany.
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    • Contributed equally to this work.

  • Torsten Hain,

    1. Institute of Medical Microbiology, Justus-Liebig-University Giessen, 35392 Giessen, Germany.
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    • Contributed equally to this work.

  • Walid Mohamed,

    1. Institute of Medical Microbiology, Justus-Liebig-University Giessen, 35392 Giessen, Germany.
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  • Brian J. Tindall,

    1. Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH (DSMZ), Inhoffenstraße 7b, 38124 Braunschweig, Germany.
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  • Manfred Nimtz,

    1. Helmholtz Centre for Infection Research, Division of Cell and Immune Biology, Cellular Proteomics Group, Inhoffenstraße 7, D-38124 Braunschweig, Germany.
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  • Trinad Chakraborty,

    Corresponding author
    1. Institute of Medical Microbiology, Justus-Liebig-University Giessen, 35392 Giessen, Germany.
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  • Jürgen Wehland,

    1. Helmholtz Centre for Infection Research, Division of Cell and Immune Biology, Cellular Proteomics Group, Inhoffenstraße 7, D-38124 Braunschweig, Germany.
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  • Lothar Jänsch

    Corresponding author
    1. Helmholtz Centre for Infection Research, Division of Cell and Immune Biology, Cellular Proteomics Group, Inhoffenstraße 7, D-38124 Braunschweig, Germany.
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*E-mail lothar.jaensch@helmholtz-hzi.de; Tel. (+49) 531 61813030; Fax (+49) 531 61817099;

**E-mail trinad.chakraborty@mikrobio.med.uni-giessen.de; Tel. (+49) 641 994 1250; Fax (+49) 641 994 1259.

Summary

Pathogenic bacteria have to cope with defence mechanisms mediated by adaptive and innate immunity of the host cells. Cationic antimicrobial peptides (CAMPs) represent one of the most effective components of the host innate immune response. Here we establish the function of Lmo1695, a member of the VirR-dependent virulence regulon, recently identified in Listeria monocytogenes. Lmo1695 encodes a membrane protein of 98 kDa with strong homology to the multiple peptide resistance factor (MprF) of Staphylococcus aureus. Like staphylococcal MprF, we found that Lmo1695 is involved in the synthesis of the membrane phospholipid lysylphosphatidylglycerol (L-PG). In addition, Lmo1695 is also essential for lysinylation of diphosphatidylglycerol (DPG), another phospholipid widely distributed in bacterial membranes. A Δlmo1695 mutant lacking the lysinylated phospholipids was particularly susceptible to CAMPs of human and bacterial origin. The mutant strain infected both epithelial cells and macrophages only poorly and was attenuated for virulence when tested in a mouse model of infection. Lmo1695 is a member of a growing list of survival factors which enable growth of L. monocytogenes in different environments.

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