Spores of Clostridioides difficile are toxin delivery vehicles.

Autor: Cassona CP; Instituto de Tecnologia Química e Biológica, NOVA University Lisbon, Oeiras, Portugal., Ramalhete S; Instituto de Tecnologia Química e Biológica, NOVA University Lisbon, Oeiras, Portugal., Amara K; Instituto de Tecnologia Química e Biológica, NOVA University Lisbon, Oeiras, Portugal., Candela T; Micalis Institute, Université Paris-Saclay, INRAE, AgroParisTech, Jouy-en-Josas, France., Kansau I; Micalis Institute, Université Paris-Saclay, INRAE, AgroParisTech, Jouy-en-Josas, France., Denève-Larrazet C; Micalis Institute, Université Paris-Saclay, INRAE, AgroParisTech, Jouy-en-Josas, France., Janoir-Jouveshomme C; Micalis Institute, Université Paris-Saclay, INRAE, AgroParisTech, Jouy-en-Josas, France., Mota LJ; Associate Laboratory i4HB, Institute for Health and Bioeconomy, NOVA School of Science and Technology, NOVA University Lisbon, Caparica, Portugal.; UCIBIO, Applied Molecular Biosciences Unit, Department of Life Sciences, NOVA School of Science and Technology, NOVA University Lisbon, Caparica, Portugal., Dupuy B; Institut Pasteur, Université Paris-Cité, UMR-CNRS 6047, Laboratoire Pathogenèse des Bactéries Anaérobies, F-75015, Paris, France., Serrano M; Instituto de Tecnologia Química e Biológica, NOVA University Lisbon, Oeiras, Portugal., Henriques AO; Instituto de Tecnologia Química e Biológica, NOVA University Lisbon, Oeiras, Portugal. aoh@itqb.unl.pt.
Jazyk: angličtina
Zdroj: Communications biology [Commun Biol] 2024 Jul 10; Vol. 7 (1), pp. 839. Date of Electronic Publication: 2024 Jul 10.
DOI: 10.1038/s42003-024-06521-x
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 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 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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