Structures and mechanisms in killing of Clostridioides (Clostridium) difficile by bacteriophages

这是一个跨学科的合作，建立在以前联合学生的工作和由BBSRC联合拨款支持的正在进行的工作的基础上。这两位申请者在细菌细胞表面成像和分子生物学的互补方法方面都有很好的记录。我们的目的是了解噬菌体与艰难梭状芽胞杆菌(以前的梭状芽孢杆菌)细胞表面(S层)结合以及随后穿透细胞膜的机制。艰难梭菌是可能致命的抗生素相关性腹泻的主要原因。现有的抗生素会加剧对肠道微生物区系的破坏，因此迫切需要针对特定物种的新疗法。我们将从结构上询问宿主受体与一系列可用的噬菌体的相互作用。了解噬菌体是如何结合和杀死细胞的，有助于设计新的非抗生素疗法。

This is a cross-disciplinary collaboration building on work by a previous joint student and ongoing work supported by a joint BBSRC grant. Both applicants have a strong track record in complementary approaches of imaging and molecular biology of bacterial cell surfaces. Our aim is to understand the mechanics of binding of bacteriophages to the Clostridioides difficile (formerly Clostridium) cell surface (S-layer) and subsequent penetration of the cell envelope. C. difficile is the leading cause of potentially fatal antibiotic-associated diarrhoea. Available antibiotics exacerbate damage to the protective gut microbiota so there is an urgent need for new species-specific treatments. We will structurally interrogate the host receptor interactions with a range of available phages. Understanding how phages bind and kill the cell could aid in the design of new non-antibiotic therapeutics.