Subtilisin-like serine protease C (CspC) (CspC)

Subtilisin-like serine protease C (CspC) is the primary molecular receptor responsible for initiating the germination of Clostridioides difficile spores in response to host signals. Although it belongs to the subtilisin-like protease family, CspC is a pseudoprotease that lacks catalytic activity and has evolved to function as a specialized receptor for bile acids, such as taurocholate, within the mammalian gut (Francis et al., 2013, Nature). Upon binding to germinants, CspC triggers a signaling cascade that activates the protease CspB, which subsequently processes the cortex-lytic enzyme SleC to allow for spore outgrowth and the transition to toxin-producing vegetative cells (Bhattacharjee et al., 2016, Scientific Reports). Because C. difficile spores are highly resistant to antibiotics and are the primary cause of disease recurrence, CspC represents a critical therapeutic target for preventing the onset of infection. Current drug development efforts focus on small molecule inhibitors and bile acid analogs that can block CspC to maintain spores in a dormant, non-pathogenic state (Kochan et al., 2017, PLOS Pathogens).

Other names

Bile acid germinant receptorClostridioides difficile spore germination receptorCspC pseudoproteaseCD1022

Inhibition of the bile acid-induced germination signaling pathway by acting as a competitive or non-competitive antagonist at the CspC receptor site.