title: Influence of PhoP and intra-species variations on virulence of Yersinia pseudotuberculosis during the natural oral infection route.
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.
authors: Department of Molecular Infection Biology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors: Fabio
authors: F
authors: Pisano
authors: Department of Molecular Infection Biology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors: Wiebke
authors: W
authors: Heine
authors: Department of Molecular Infection Biology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors: Maik
authors: M
authors: Rosenheinrich
authors: Department of Molecular Infection Biology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors: Janina
authors: J
authors: Schweer
authors: Department of Molecular Infection Biology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors: Aaron M
authors: AM
authors: Nuss
authors: Department of Molecular Infection Biology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors: Petra
authors: P
authors: Dersch
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002470:Cell Survival; D018925:Chemokines / Q000097:blood; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D007113:Immunity, Innate; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009059:Mouth Diseases / Q000276:immunology / Q000382:microbiology / Q000473:pathology*; D009154:Mutation; D013154:Spleen / Q000166:cytology / Q000276:immunology; D014774:Virulence; D015011:Yersinia pseudotuberculosis / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology*; D015012:Yersinia pseudotuberculosis Infections / Q000276:immunology / Q000401:mortality / Q000473:pathology
chemical_list: D001426:Bacterial Proteins; D018925:Chemokines; D016207:Cytokines; C079792:PhoQ protein, Bacteria; C061064:PhoP protein, Bacteria