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

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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.