Pickering Amy C, Fitzgerald J Ross
The Roslin Institute and Edinburgh Infectious Diseases, University of Edinburgh, Easter Bush Campus, Edinburgh, United Kingdom.
Front Microbiol. 2020 Oct 29;11:594737. doi: 10.3389/fmicb.2020.594737. eCollection 2020.
Gram-positive bacterial pathogens have an array of proteins on their cell surface that mediate interactions with the host environment. In particular, bacterial cell wall-associated (CWA) proteins play key roles in both colonization and pathogenesis. Furthermore, some CWA proteins promote specialization for host-species or mediate colonization of specific anatomical niches within a host. In this mini review, we provide examples of the many ways by which major pathogens, such as Staphylococci, Streptococci and , utilize CWA proteins for both host- and niche-specialization. We describe different biological mechanisms mediated by CWA proteins including: the acquisition of iron from hemoglobin in the bloodstream, adherence to and invasion of host cells, and innate immune evasion through binding to the plasma proteins fibrinogen, immunoglobulin G, and complement. We also discuss the limitations of using animal models for understanding the role of specific CWA proteins in host-specialization and how transformative technologies, such as CRISPR-Cas, offer tremendous potential for developing transgenic models that simulate the host environment of interest. Improved understanding of the role of CWA proteins in niche- or host-specificity will allow the design of new therapeutic approaches which target key host-pathogen interactions underpinning Gram-positive bacterial infections.
革兰氏阳性菌病原体在其细胞表面有一系列蛋白质，介导与宿主环境的相互作用。特别是，细菌细胞壁相关（CWA）蛋白在定植和发病机制中都起着关键作用。此外，一些CWA蛋白促进对宿主物种的特异性适应或介导在宿主体内特定解剖学微环境的定植。在这篇小型综述中，我们列举了葡萄球菌、链球菌等主要病原体利用CWA蛋白实现宿主和微环境特异性的多种方式。我们描述了由CWA蛋白介导的不同生物学机制，包括：从血液中的血红蛋白获取铁、黏附并侵入宿主细胞，以及通过与血浆蛋白纤维蛋白原、免疫球蛋白G和补体结合来逃避固有免疫。我们还讨论了使用动物模型来理解特定CWA蛋白在宿主特异性中的作用的局限性，以及诸如CRISPR-Cas等变革性技术如何为开发模拟感兴趣的宿主环境的转基因模型提供巨大潜力。对CWA蛋白在微环境或宿主特异性中的作用有更深入的了解，将有助于设计针对革兰氏阳性菌感染背后关键宿主-病原体相互作用的新治疗方法。
