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

Pisano F, Heine W, Rosenheinrich M, Schweer J, Nuss AM, Dersch P - PLoS ONE (2014)

Bottom Line: 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.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.Highlighted intra-species variations may provide a potential means to rapidly adjust to environmental changes inside and outside of the host.

View Article: PubMed Central - PubMed

Affiliation: 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.

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Colonization of Y. pseudotuberculosis YPIII (phoP−), YP149 (YPIII phoP+), IP32953 (phoP+) and YPIP06 (IP32953 phoP−) in host tissues.BALB/c mice were challenged with 2×108 CFU of Y. pseudotuberculosis strains YPIII (phoP−) (n = 15), YP149 (YPIII phoP+) (n = 15), IP32953 (phoP+) (n = 15) and YPIP06 (IP32953 phoP−) (n = 15). At day 3 postinfection mice were sacrificed. Numbers of bacteria cells from the different strains were determined in the lymphatic organs PPs (A), MLNs (B) and the systemic organs liver (C) and spleen (D). Data from four independent experiments were pooled. Bacterial loads were compared using One-way ANOVA with Tukey’s post hoc test (*, p<0.05; **, p<0.01; ***, p<0.001).
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pone-0103541-g003: Colonization of Y. pseudotuberculosis YPIII (phoP−), YP149 (YPIII phoP+), IP32953 (phoP+) and YPIP06 (IP32953 phoP−) in host tissues.BALB/c mice were challenged with 2×108 CFU of Y. pseudotuberculosis strains YPIII (phoP−) (n = 15), YP149 (YPIII phoP+) (n = 15), IP32953 (phoP+) (n = 15) and YPIP06 (IP32953 phoP−) (n = 15). At day 3 postinfection mice were sacrificed. Numbers of bacteria cells from the different strains were determined in the lymphatic organs PPs (A), MLNs (B) and the systemic organs liver (C) and spleen (D). Data from four independent experiments were pooled. Bacterial loads were compared using One-way ANOVA with Tukey’s post hoc test (*, p<0.05; **, p<0.01; ***, p<0.001).

Mentions: Upon oral infection, Y. pseudotuberculosis disseminates from the PPs and/or small intestinal epithelium to the MLNs and systemic organs like the liver and spleen. To explain the observed virulence properties in the oral infection model, we investigated the influence of PhoP on colonization and dissemination of YPIII and IP32953 in more detail. For each strain, mice were orally challenged with 2×108 CFUs. At day 3 postinfection, mice were sacrificed and the bacterial burden in the PPs, MLNs, spleen and liver was assessed (Fig. 3). Analysis of the organ burden revealed significant strain specific differences in the colonization and dissemination ability. IP32953 and IP32953 phoP− populated all assessed organs with higher efficiency than YPIII and YPIII phoP+ (Fig. 3). Furthermore, the YPIII and YPIII phoP+ strains disseminated less efficiently to the MLNs, liver and spleen (Fig. 3). Despite the small differences observed for the survival of the mice (Fig. 2), organ colonization by YPIII was not affected by the presence of a functional copy of phoP. Indeed, YPIII phoP+ and YPIII phoP− bacteria were found at similar levels in all analyzed organs. In contrast, the lymphatic tissues (PPs and MLNs) were populated slightly more efficiently by IP32953 in the absence of a functional PhoP (Fig. 3A, B), while less bacteria were isolated from the liver and spleen (Fig. 3C, D). In summary, this data indicates that PhoP appears to be dispensable for host tissue colonization by YPIII, and only minor changes were observed for IP32953.


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

Pisano F, Heine W, Rosenheinrich M, Schweer J, Nuss AM, Dersch P - PLoS ONE (2014)

Colonization of Y. pseudotuberculosis YPIII (phoP−), YP149 (YPIII phoP+), IP32953 (phoP+) and YPIP06 (IP32953 phoP−) in host tissues.BALB/c mice were challenged with 2×108 CFU of Y. pseudotuberculosis strains YPIII (phoP−) (n = 15), YP149 (YPIII phoP+) (n = 15), IP32953 (phoP+) (n = 15) and YPIP06 (IP32953 phoP−) (n = 15). At day 3 postinfection mice were sacrificed. Numbers of bacteria cells from the different strains were determined in the lymphatic organs PPs (A), MLNs (B) and the systemic organs liver (C) and spleen (D). Data from four independent experiments were pooled. Bacterial loads were compared using One-way ANOVA with Tukey’s post hoc test (*, p<0.05; **, p<0.01; ***, p<0.001).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4116203&req=5

pone-0103541-g003: Colonization of Y. pseudotuberculosis YPIII (phoP−), YP149 (YPIII phoP+), IP32953 (phoP+) and YPIP06 (IP32953 phoP−) in host tissues.BALB/c mice were challenged with 2×108 CFU of Y. pseudotuberculosis strains YPIII (phoP−) (n = 15), YP149 (YPIII phoP+) (n = 15), IP32953 (phoP+) (n = 15) and YPIP06 (IP32953 phoP−) (n = 15). At day 3 postinfection mice were sacrificed. Numbers of bacteria cells from the different strains were determined in the lymphatic organs PPs (A), MLNs (B) and the systemic organs liver (C) and spleen (D). Data from four independent experiments were pooled. Bacterial loads were compared using One-way ANOVA with Tukey’s post hoc test (*, p<0.05; **, p<0.01; ***, p<0.001).
Mentions: Upon oral infection, Y. pseudotuberculosis disseminates from the PPs and/or small intestinal epithelium to the MLNs and systemic organs like the liver and spleen. To explain the observed virulence properties in the oral infection model, we investigated the influence of PhoP on colonization and dissemination of YPIII and IP32953 in more detail. For each strain, mice were orally challenged with 2×108 CFUs. At day 3 postinfection, mice were sacrificed and the bacterial burden in the PPs, MLNs, spleen and liver was assessed (Fig. 3). Analysis of the organ burden revealed significant strain specific differences in the colonization and dissemination ability. IP32953 and IP32953 phoP− populated all assessed organs with higher efficiency than YPIII and YPIII phoP+ (Fig. 3). Furthermore, the YPIII and YPIII phoP+ strains disseminated less efficiently to the MLNs, liver and spleen (Fig. 3). Despite the small differences observed for the survival of the mice (Fig. 2), organ colonization by YPIII was not affected by the presence of a functional copy of phoP. Indeed, YPIII phoP+ and YPIII phoP− bacteria were found at similar levels in all analyzed organs. In contrast, the lymphatic tissues (PPs and MLNs) were populated slightly more efficiently by IP32953 in the absence of a functional PhoP (Fig. 3A, B), while less bacteria were isolated from the liver and spleen (Fig. 3C, D). In summary, this data indicates that PhoP appears to be dispensable for host tissue colonization by YPIII, and only minor changes were observed for IP32953.

Bottom Line: 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.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.Highlighted intra-species variations may provide a potential means to rapidly adjust to environmental changes inside and outside of the host.

View Article: PubMed Central - PubMed

Affiliation: 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.

Show MeSH
Related in: MedlinePlus