Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI, USA.
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.
Nat Microbiol. 2020 Sep;5(9):1170-1181. doi: 10.1038/s41564-020-0746-5. Epub 2020 Jun 29.
A variety of cell surface structures dictate interactions between bacteria and their environment, including their viruses (bacteriophages). Members of the human gut Bacteroidetes characteristically produce several phase-variable capsular polysaccharides (CPSs), but their contributions to bacteriophage interactions are unknown. To begin to understand how CPSs have an impact on Bacteroides-phage interactions, we isolated 71 Bacteroides thetaiotaomicron-infecting bacteriophages from two locations in the United States. Using B. thetaiotaomicron strains that express defined subsets of CPSs, we show that CPSs dictate host tropism for these phages and that expression of non-permissive CPS variants is selected under phage predation, enabling survival. In the absence of CPSs, B. thetaiotaomicron escapes bacteriophage predation by altering expression of eight distinct phase-variable lipoproteins. When constitutively expressed, one of these lipoproteins promotes resistance to multiple bacteriophages. Our results reveal important roles for Bacteroides CPSs and other cell surface structures that allow these bacteria to persist under bacteriophage predation, and hold important implications for using bacteriophages therapeutically to target gut symbionts.
各种细胞表面结构决定了细菌与其环境之间的相互作用，包括它们的病毒（噬菌体）。人类肠道拟杆菌的特征是产生几种可相变化的荚膜多糖（CPS），但其对噬菌体相互作用的贡献尚不清楚。为了开始了解 CPS 如何影响拟杆菌-噬菌体相互作用，我们从美国的两个地点分离了 71 株感染双歧杆菌的噬菌体。使用表达特定 CPS 子集的双歧杆菌菌株，我们表明 CPS 决定了这些噬菌体的宿主趋向性，并且在噬菌体捕食下，非允许性 CPS 变体的表达被选择，从而使细菌得以存活。在没有 CPS 的情况下，双歧杆菌通过改变八种不同的相变化脂蛋白的表达来逃避噬菌体的捕食。当这些脂蛋白被组成性表达时，其中一种脂蛋白可以促进对多种噬菌体的抗性。我们的研究结果揭示了拟杆菌 CPS 和其他细胞表面结构的重要作用，这些结构使这些细菌能够在噬菌体捕食下持续存在，并对使用噬菌体治疗来靶向肠道共生菌具有重要意义。
