Fight or flee, a vital choice for Clostridioides difficile

Abstract

Clostridioides difficile is a leading cause of healthcare-associated infections, causing billions of economic losses every year. Its symptoms range from mild diarrhea to life-threatening damage to the colon. Transmission and recurrence of C. difficile infection (CDI) are mediated by the metabolically dormant spores, while the virulence of C. difficile is mainly due to the two large clostridial toxins, TcdA and TcdB. Producing toxins or forming spores are two different strategies for C. difficile to cope with harsh environmental conditions. It is of great significance to understand the molecular mechanisms for C. difficile to skew to either of the cellular processes. Here, we summarize the current understanding of the regulation and connections between toxin production and sporulation in C. difficile and further discuss the potential solutions for yet-to-be-answered questions.

Keywords: C. difficile; TcdA; TcdB; sporulation; toxin production.

Figure 1

The regulatory network between sporulation and toxin production. The central panel depicts important regulatory factors. CcpA, CodY, and SinR tune sporulation and toxin production codirectionally, while SigD, SigH, RstA, and Agr1 tune these two processes differentially. TcdR and Spo0A possibly suppress each other. Arrows indicate upregulation; the blunt ended line indicates downregulation; the dashed line indicates uncertainty or conflict reports. The left panel depicts the Clostridioides difficile PaLoc and the domains of TcdA and TcdB. The right panel depicts the stage II to stage VII of spore formation and the regulators in the forespore and mother cell.