Spo0A differentially regulates toxin production in evolutionarily diverse strains of Clostridium difficile.

Clostridium difficile is an important pathogen of humans and animals, representing a significant global healthcare problem. The last decade has seen the emergence of epidemic BI/NAP1/027 and ribotype 078 isolates, associated with the onset of more severe disease and higher rates of morbidity and mor...

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Autores principales:	Kate E Mackin, Glen P Carter, Pauline Howarth, Julian I Rood, Dena Lyras
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b818626fb88f442f81344258784f0b7c
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spelling	oai:doaj.org-article:b818626fb88f442f81344258784f0b7c2021-11-18T08:46:44ZSpo0A differentially regulates toxin production in evolutionarily diverse strains of Clostridium difficile.1932-620310.1371/journal.pone.0079666https://doaj.org/article/b818626fb88f442f81344258784f0b7c2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24236153/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Clostridium difficile is an important pathogen of humans and animals, representing a significant global healthcare problem. The last decade has seen the emergence of epidemic BI/NAP1/027 and ribotype 078 isolates, associated with the onset of more severe disease and higher rates of morbidity and mortality. However, little is known about these isolates at the molecular level, partly due to difficulties in the genetic manipulation of these strains. Here we report the development of an optimised Tn916-mediated plasmid transfer system, and the use of this system to construct and complement spo0A mutants in a number of different C. difficile strain backgrounds. Spo0A is a global regulator known to control sporulation, but may also be involved in the regulation of potential virulence factors and other phenotypes. Recent studies have failed to elucidate the role of Spo0A in toxin A and toxin B production by C. difficile, with conflicting data published to date. In this study, we aimed to clarify the role of Spo0A in production of the major toxins by C. difficile. Through the construction and complementation of spo0A mutants in two ribotype 027 isolates, we demonstrate that Spo0A acts as a negative regulator of toxin A and toxin B production in this strain background. In addition, spo0A was disrupted and subsequently complemented in strain 630Δerm and, for the first time, in a ribotype 078 isolate, JGS6133. In contrast to the ribotype 027 strains, Spo0A does not appear to regulate toxin production in strain 630Δerm. In strain JGS6133, Spo0A appears to negatively regulate toxin production during early stationary phase, but has little effect on toxin expression during late stationary phase. These data suggest that Spo0A may differentially regulate toxin production in phylogenetically distinct C. difficile strain types. In addition, Spo0A may be involved in regulating some aspects of C. difficile motility.Kate E MackinGlen P CarterPauline HowarthJulian I RoodDena LyrasPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 11, p e79666 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kate E Mackin Glen P Carter Pauline Howarth Julian I Rood Dena Lyras Spo0A differentially regulates toxin production in evolutionarily diverse strains of Clostridium difficile.
description	Clostridium difficile is an important pathogen of humans and animals, representing a significant global healthcare problem. The last decade has seen the emergence of epidemic BI/NAP1/027 and ribotype 078 isolates, associated with the onset of more severe disease and higher rates of morbidity and mortality. However, little is known about these isolates at the molecular level, partly due to difficulties in the genetic manipulation of these strains. Here we report the development of an optimised Tn916-mediated plasmid transfer system, and the use of this system to construct and complement spo0A mutants in a number of different C. difficile strain backgrounds. Spo0A is a global regulator known to control sporulation, but may also be involved in the regulation of potential virulence factors and other phenotypes. Recent studies have failed to elucidate the role of Spo0A in toxin A and toxin B production by C. difficile, with conflicting data published to date. In this study, we aimed to clarify the role of Spo0A in production of the major toxins by C. difficile. Through the construction and complementation of spo0A mutants in two ribotype 027 isolates, we demonstrate that Spo0A acts as a negative regulator of toxin A and toxin B production in this strain background. In addition, spo0A was disrupted and subsequently complemented in strain 630Δerm and, for the first time, in a ribotype 078 isolate, JGS6133. In contrast to the ribotype 027 strains, Spo0A does not appear to regulate toxin production in strain 630Δerm. In strain JGS6133, Spo0A appears to negatively regulate toxin production during early stationary phase, but has little effect on toxin expression during late stationary phase. These data suggest that Spo0A may differentially regulate toxin production in phylogenetically distinct C. difficile strain types. In addition, Spo0A may be involved in regulating some aspects of C. difficile motility.
format	article
author	Kate E Mackin Glen P Carter Pauline Howarth Julian I Rood Dena Lyras
author_facet	Kate E Mackin Glen P Carter Pauline Howarth Julian I Rood Dena Lyras
author_sort	Kate E Mackin
title	Spo0A differentially regulates toxin production in evolutionarily diverse strains of Clostridium difficile.
title_short	Spo0A differentially regulates toxin production in evolutionarily diverse strains of Clostridium difficile.
title_full	Spo0A differentially regulates toxin production in evolutionarily diverse strains of Clostridium difficile.
title_fullStr	Spo0A differentially regulates toxin production in evolutionarily diverse strains of Clostridium difficile.
title_full_unstemmed	Spo0A differentially regulates toxin production in evolutionarily diverse strains of Clostridium difficile.
title_sort	spo0a differentially regulates toxin production in evolutionarily diverse strains of clostridium difficile.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/b818626fb88f442f81344258784f0b7c
work_keys_str_mv	AT kateemackin spo0adifferentiallyregulatestoxinproductioninevolutionarilydiversestrainsofclostridiumdifficile AT glenpcarter spo0adifferentiallyregulatestoxinproductioninevolutionarilydiversestrainsofclostridiumdifficile AT paulinehowarth spo0adifferentiallyregulatestoxinproductioninevolutionarilydiversestrainsofclostridiumdifficile AT julianirood spo0adifferentiallyregulatestoxinproductioninevolutionarilydiversestrainsofclostridiumdifficile AT denalyras spo0adifferentiallyregulatestoxinproductioninevolutionarilydiversestrainsofclostridiumdifficile
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Spo0A differentially regulates toxin production in evolutionarily diverse strains of Clostridium difficile.

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