Model for Clostridioides difficile germination. Top: Model of the C. difficile proteins required for germination during sporulation. From left to right: interdomain processing of the CspBA fusion protein by the protease YabG occurs in the spore coat layer; heterodimerization of CspC and CspA and homodimerization of CspB; and loading of key germination proteins into the cortex region of the mature spore. Bottom right: Model of a C. difficile spore undergoing germination. Sensing of germinant and co-germinant signals (either directly or indirectly) by the CspC:CspA heterodimer (1) leads to the heterodimer adopting an active conformation (2). Bottom left: CspC:CspA heterodimer space-filling model. Residues at the center of the CspC:CspA heterodimer binding interface (I.) play important roles in transducing germinant and co-germinant signals, while residues at the periphery of the binding interface (II.) help stabilize the complex. Signal transduction by the CspC:CspA heterodimer initiates the activation of CspB (either directly or indirectly) (3). Active CspB then proteolytically activates the cortex-lytic enzyme SleC (4), which will go on to degrade the spore cortex (5), allowing for rehydration of the spore core and resumption of metabolic activity.
Unlike other #bacteria, C. difficile must detect both germinant & co-germinant signals to trigger #spore #germination. This study finds that the CspC:CspA complex is a key signaling node that integrates environmental cues to regulate #Cdifficile spore germination @plosbiology.org 🧪 plos.io/4rtCKdZ
