SUMMARY The bacterial pathogen, Clostridioides difficile, has been designated an urgent threat to the US healthcare system by the Centers for Disease Control. In order for C. difficile to initiate infection, its infectious spore form must germinate in the gut of susceptible individuals. Since spore germination depends on the spore cell wall undergoing specific modifications, determining how this process occurs in C. difficile could inform the development of strategies for preventing C. difficile disease transmission and recurrence.