Influence of PhoP and intra-species variations on virulence of Yersinia pseudotuberculosis during the natural oral infection route

Fabio Pisano; Wiebke Heine; Maik Rosenheinrich; Janina Schweer; Aaron M Nuss; Petra Dersch

doi:10.1371/journal.pone.0103541

Influence of PhoP and intra-species variations on virulence of Yersinia pseudotuberculosis during the natural oral infection route

PLoS One. 2014 Jul 30;9(7):e103541. doi: 10.1371/journal.pone.0103541. eCollection 2014.

Authors

Fabio Pisano¹, Wiebke Heine¹, Maik Rosenheinrich¹, Janina Schweer¹, Aaron M Nuss¹, Petra Dersch¹

Affiliation

¹ Department of Molecular Infection Biology, Helmholtz Centre for Infection Research, Braunschweig, Germany.

Abstract

The two-component regulatory system PhoP/PhoQ has been shown to (i) control expression of virulence-associated traits, (ii) confer survival and growth within macrophages and (iii) play a role in Yersinia infections. However, the influence of PhoP on virulence varied greatly between different murine models of infection and its role in natural oral infections with frequently used representative isolates of Y. pseudotuberculosis was unknown. To address this issue, we constructed an isogenic set of phoP+ and phoP- variants of strain IP32953 and YPIII and analyzed the impact of PhoP using in vitro functionality experiments and a murine oral infection model, whereby we tested for bacterial dissemination and influence on the host immune response. Our results revealed that PhoP has a low impact on virulence, lymphatic and systemic organ colonization, and on immune response modulation by IP32953 and YPIII, indicating that PhoP is not absolutely essential for oral infections but may be involved in fine-tuning the outcome. Our work further revealed certain strain-specific differences in virulence properties, which do not strongly rely on the function of PhoP, but affect tissue colonization, dissemination and/or persistence of the bacteria. Highlighted intra-species variations may provide a potential means to rapidly adjust to environmental changes inside and outside of the host.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adaptive Immunity
Animals
Bacterial Proteins / genetics
Bacterial Proteins / metabolism*
Cell Line
Cell Survival
Chemokines / blood
Cytokines / blood
Disease Models, Animal
Female
Immunity, Innate
Macrophages / cytology
Macrophages / metabolism
Mice
Mice, Inbred BALB C
Mouth Diseases / immunology
Mouth Diseases / microbiology
Mouth Diseases / pathology*
Mutation
Spleen / cytology
Spleen / immunology
Virulence
Yersinia pseudotuberculosis / genetics
Yersinia pseudotuberculosis / pathogenicity*
Yersinia pseudotuberculosis / physiology*
Yersinia pseudotuberculosis Infections / immunology
Yersinia pseudotuberculosis Infections / mortality
Yersinia pseudotuberculosis Infections / pathology

Substances

Bacterial Proteins
Chemokines
Cytokines
PhoQ protein, Bacteria
PhoP protein, Bacteria

Grants and funding

This work was supported by the Deutsche Forschungsgemeinschaft Grants DE616/4-2 (SPP1316) for AN, a stipend of the President’s Initiative and Network Fund of the Helmholtz Association of German Research Centres (HGF) (VH-GS-202) for WH, a stipend of the DFG funded IRTG1273, the Deutsche Zentrum für Infektionsforschung (DZIF) for FP and PD, and the Fonds der Chemischen Industrie for PD. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.