Spores of Clostridioides difficile are toxin delivery vehicles.

Autor: Cassona, Carolina P., Ramalhete, Sara, Amara, Khira, Candela, Thomas, Kansau, Imad, Denève-Larrazet, Cécile, Janoir-Jouveshomme, Claire, Mota, Luís Jaime, Dupuy, Bruno, Serrano, Mónica, Henriques, Adriano O.
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Zdroj: Communications Biology; 7/10/2024, Vol. 7 Issue 1, p1-17, 17p
Abstrakt: 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 σD, which primes the TcdR auto-regulatory loop. In contrast, the forespore-specific regulatory proteins σG 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 ΔtcdA or ΔtcdB spores but not ΔtcdR or ΔtcdA/ΔtcdB 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. This study shows that the genes coding for the two main toxins produced by Clostridioides difficile are expressed during sporulation and that the toxins associate with the mature spores, which have a cytopathic effect on human intestinal cell lines. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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