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

这是一个跨学科的合作，建立在以前的联合学生的工作和正在进行的工作由联合BBSRC赠款支持。两个申请人在细菌细胞表面的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菌（以前的梭菌）细胞表面（S层）的结合机制以及随后的细胞包膜渗透。C.艰难梭菌是潜在致死性腹泻相关腹泻的主要原因。可用的抗生素加剧了对保护性肠道微生物群的损害，因此迫切需要新的物种特异性治疗。我们将从结构上询问宿主受体与一系列可用的受体的相互作用。了解抗生素如何结合和杀死细胞可以帮助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.