2012
DOI: 10.1128/iai.00147-12
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The Clostridium difficile spo0A Gene Is a Persistence and Transmission Factor

Abstract: dClostridium difficile is a major cause of chronic antibiotic-associated diarrhea and a significant health care-associated pathogen that forms highly resistant and infectious spores. Spo0A is a highly conserved transcriptional regulator that plays a key role in initiating sporulation in Bacillus and Clostridium species. Here, we use a murine model to study the role of the C. difficile spo0A gene during infection and transmission. We demonstrate that C. difficile spo0A mutant derivatives can cause intestinal di… Show more

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Cited by 332 publications
(420 citation statements)
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“…difficile spores are well known to be important contributors to the pathogenesis of CDI (1, 3). Indeed, the C. difficile ⌬spo0A strain, incapable of forming spores, was unable to persist in a murine model (4). It has been suggested that persistence of C. difficile in the host might be mediated through the adherence of C. difficile spores to the host's intestinal epithelium (7) and by surviving attacks of phagocytic cells (36).…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…difficile spores are well known to be important contributors to the pathogenesis of CDI (1, 3). Indeed, the C. difficile ⌬spo0A strain, incapable of forming spores, was unable to persist in a murine model (4). It has been suggested that persistence of C. difficile in the host might be mediated through the adherence of C. difficile spores to the host's intestinal epithelium (7) and by surviving attacks of phagocytic cells (36).…”
Section: Discussionmentioning
confidence: 99%
“…During the infection cycle, C. difficile begins a sporulation process, where at least part of the spores are believed to remain adhered to the colonic surfaces and the rest are released to the environment through the feces. Indeed, studies in a mouse model system have demonstrated that sporulation-deficient strains are incapable of producing recurrence and persistence of C. difficile in the infected mouse and transmission to neighboring mice (4), indicating that spore formation during CDI is essential for persistence and transmission. This is consistent with the fact that once antibiotic treatment for CDI has been discontinued, the majority of the patients continue shedding C. difficile spores for up to 2 weeks (5), highlighting the role that C. difficile spores play in C. difficile pathogenesis (1,3).…”
mentioning
confidence: 99%
“…Inactivating Spo0A, the master regulator of sporulation in Clostridium species [63 ], was thought to be the obvious strategy for abolishing sporulation [64]. However, Spo0A's involvement in solvent production [65,66] and biofilm formation [62,63 ,67] will necessitate tuned expression rather than complete inactivation. Alternatively, sporulation regulators downstream to Spo0A can be targeted for creating asporogenous strains, as was demonstrated for C. acetobutylicum [64] and C. phytofermentans [68].…”
Section: Strain Engineering To Obtain Desired Production Phenotypesmentioning
confidence: 99%
“…Recientemente, Deakinet y cols. 37 , demostraron que cepas de C. difficile que no forman esporas, producto de una mutación en el regulador maestro de esporulación, spo0A, son incapaces de persistir y diseminarse en un modelo murino de IACD.…”
Section: Formación De La Espora De C Difficile Durante La Iacdunclassified
“…A pesar de que no existe evidencia directa de esporulación y persistencia de esporas de C. difficile en el tracto colónico de humanos, es posible que estos procesos sean similares a los reportados en modelos murinos 36,37 . Estos datos concuerdan con estudios clínicos donde 50% de los pacientes que se recuperan de un episodio de IACD se convierten en diseminadores asintomáticos de sus esporas por un período de 1-4 semanas después de la antibioterapia 26,38 .…”
Section: Formación De La Espora De C Difficile Durante La Iacdunclassified