Influence of PhoP and intra-species variations on virulence of Yersinia pseudotuberculosis during the natural oral infection route.
Influence of PhoP and intra-species variations on virulence of Yersinia pseudotuberculosis during the natural oral infection route.
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DOI：
10.1371/journal.pone.0103541
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Dersch P
中科院分区：
文献类型：
--
作者：
Pisano F;Heine W;Rosenheinrich M;Schweer J;Nuss AM;Dersch P
双组分调控系统PhoP/PhoQ已被证明（i）控制毒力相关性状的表达，（ii）赋予巨噬细胞内的存活和生长，以及（iii）在耶尔森氏菌感染中发挥作用。然而，PhoP对毒力的影响在不同的小鼠感染模型之间差异很大，并且其在常用的代表性Y.假结核未知。为了解决这个问题，我们构建了菌株IP 32953和YPIII的phoP +和phoP −变体的等基因组，并使用体外功能性实验和小鼠口腔感染模型分析了PhoP的影响，从而测试了细菌传播和对宿主免疫反应的影响。我们的研究结果显示，PhoP对毒力、淋巴和全身器官定植以及IP 32953和YPIII对免疫反应的调节影响很小，这表明PhoP对口腔感染并不是绝对必要的，但可能参与了结果的微调。我们的工作进一步揭示了某些菌株特异性毒力特性的差异，这些差异并不强烈依赖于PhoP的功能，但会影响细菌的组织定殖、传播和/或持久性。突出显示的种内变异可能提供一种潜在的手段，以迅速适应宿主内外的环境变化。
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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