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Bacteria that reside in the gastrointestinal tract of healthy humans are essential for our health, sustenance and well-being. About 50–60% of those bacteria have the ability to produce resilient spores that are important for the life cycle in the gut and for host-to-host transmission. A genomic signature for sporulation in the human intestine was recently described, which spans both commensals and pathogens such as  Clostridioides difficile  and contains several genes of unknown function. We report on the characterization of a signature gene,  CD25890 , which, as we show is involved in the control of sporulation initiation in  C. difficile  under certain nutritional conditions. Spo0A is the main regulatory protein controlling entry into sporulation and we show that an in-frame deletion of  CD25890  results in increased expression of  spo0A  per cell and increased sporulation. The effect of CD25890 on  spo0A  is likely indirect and mediated through repression of the  sinRR ´ operon. Deletion of the  CD25890  gene, however, does not alter the expression of the genes coding for the cytotoxins or the genes involved in biofilm formation. Our results suggest that CD25890 acts to modulate sporulation in response to the nutrients present in the environment.

CD25890, a conserved protein that modulates sporulation initiation in Clostridioides difficile