A Revised Understanding of Clostridioides difficile Spore Germination

The dormant resistant spores of Clostridioides difficile are transformed into metabolically active cells through the process of germination. Spore germination in C. difficile is regulated by the detection of bile salt germinants and amino acid cogerminants by pseudoproteases CspC and CspA, respectively. The germinant signal is transduced to the serine protease CspB, which processes the cortex lytic enzyme SleC, leading to degradation of the spore cortex peptidoglycan and subsequent reactivation of the spore. Divergent C. difficile germination models have been proposed to explain interactions between key regulators and transduction of germinant and cogerminant signals. This review summarises advances in understanding C. difficile germination and outlines current models of germination regulation.