Yersinia pseudotuberculosis uses Ail and YadA to circumvent neutrophils by directing Yop translocation during lung infection

Authors

  • Michelle K. Paczosa,

    1. Graduate Program in Immunology, MERGE-ID Track, Sackler School of Biomedical Sciences, Tufts University, Boston, MA, USA
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    • These authors contributed equally to this work.
  • Michael L. Fisher,

    1. Graduate Program in Molecular Microbiology, Sackler School of Biomedical Sciences, Tufts University, Boston, MA, USA
    Current affiliation:
    1. Center for Infectious Diseases and Vaccinology, The Biodesign Institute at Arizona State University, Tempe, AZ, USA
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    • These authors contributed equally to this work.
  • Francisco J. Maldonado-Arocho,

    1. Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA, USA
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  • Joan Mecsas

    Corresponding author
    1. Graduate Program in Immunology, MERGE-ID Track, Sackler School of Biomedical Sciences, Tufts University, Boston, MA, USA
    2. Graduate Program in Molecular Microbiology, Sackler School of Biomedical Sciences, Tufts University, Boston, MA, USA
    3. Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA, USA
    • For correspondence. E-mail joan.mecsas@tufts.edu; Tel. (+1) 617 636 2742; Fax (+1) 617 636 0337.

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Summary

A Yersinia pseudotuberculosis (Yptb) murine model of lung infection was previously developed using the serotype III IP2666NdeI strain, which robustly colonized lungs but only sporadically disseminated to the spleen and liver. We demonstrate here that a serotype Ib Yptb strain, IP32953, colonizes the lungs at higher levels and disseminates more efficiently to the spleen and liver compared with IP2666NdeI. The role of adhesins was investigated during IP32953 lung infection by constructing isogenic Δail, Δinv, ΔpsaE and ΔyadA mutants. An IP32953ΔailΔyadA mutant initially colonized but failed to persist in the lungs and disseminate to the spleen and liver. Yptb expressing these adhesins selectively bound to and targeted neutrophils for translocation of Yops. This selective targeting was critical for virulence because persistence of the ΔailΔyadA mutant was restored following intranasal infection of neutropenic mice. Furthermore, Ail and YadA prevented killing by complement-mediated mechanisms during dissemination to and/or growth in the spleen and liver, but not in the lungs. Combined, these results demonstratethat Ail and YadA are critical, redundant virulence factors during lung infection, because they thwart neutrophils by directing Yop-translocation specifically into these cells.

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