<i>Clostridioides difficile</i>'s virulence requires efficient holin-mediated toxin secretion.

ABSTRACT: The human pathogen Clostridioides difficile causes pseudomembranous colitis through release of the potent TcdA and TcdB toxins. These toxins lack canonical N-terminal secretion signal sequences for translocation across the bacterial membrane, suggesting alternate mechanisms of release including targeted secretion mediated by the holin-like protein TcdE and passive release from cell lysis. Here, we show how the lack of the TcdE holin profoundly reduces toxin secretion in the high toxin-producing strains UK1 and VPI10463, independently of cell lysis. Remarkably, tcdE deletion in either strain rescued highly susceptible gnotobiotic mice from lethal infection. ΔtcdE-infected mice demonstrated undetectable levels of toxin acutely and long-term survival, despite active toxin

SUBMITTER: DiBenedetto NV 

PROVIDER: S-EPMC12150058 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature