Article Dans Une Revue Communications Biology Année : 2024

Spores of Clostridioides difficile are toxin delivery vehicles

Résumé

Abstract Clostridioides difficile causes a wide range of intestinal diseases through the action of two main cytotoxins, TcdA and TcdB. Ingested spores germinate in the intestine establishing a population of cells that produce toxins and spores. The pathogenicity locus, PaLoc, comprises several genes, including those coding for TcdA/B, for the holin-like TcdE protein, and for TcdR, an auto-regulatory RNA polymerase sigma factor essential for tcdA / B and tcdE expression. Here we show that tcdR , tcdA , tcdB and tcdE are expressed in a fraction of the sporulating cells, in either the whole sporangium or in the forespore. The whole sporangium pattern is due to protracted expression initiated in vegetative cells by σ D , which primes the TcdR auto-regulatory loop. In contrast, the forespore-specific regulatory proteins σ G and SpoVT control TcdR production and tcdA/tcdB and tcdE expression in this cell. We detected TcdA at the spore surface, and we show that wild type and Δ tcdA or Δ tcdB spores but not Δ tcdR or Δ tcdA/ Δ tcdB spores are cytopathic against HT29 and Vero cells, indicating that spores may serve as toxin-delivery vehicles. Since the addition of TcdA and TcdB enhance binding of spores to epithelial cells, this effect may occur independently of toxin production by vegetative cells.

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hal-04664956 , version 1 (02-04-2025)

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Carolina Cassona, Sara Ramalhete, Khira Amara, Thomas Candela, Imad Kansau, et al.. Spores of Clostridioides difficile are toxin delivery vehicles. Communications Biology, 2024, 7 (1), pp.839. ⟨10.1038/s42003-024-06521-x⟩. ⟨hal-04664956⟩
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