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Media type:
E-Article
Title:
Characterization of the Sporulation Initiation Pathway of Clostridium difficile and Its Role in Toxin Production
Contributor:
Underwood, Sarah;
Guan, Shuang;
Vijayasubhash, Vinod;
Baines, Simon D.;
Graham, Luke;
Lewis, Richard J.;
Wilcox, Mark H.;
Stephenson, Keith
Published:
American Society for Microbiology, 2009
Published in:
Journal of Bacteriology, 191 (2009) 23, Seite 7296-7305
Language:
English
DOI:
10.1128/jb.00882-09
ISSN:
0021-9193;
1098-5530
Origination:
Footnote:
Description:
<jats:title>ABSTRACT</jats:title>
<jats:p>
<jats:italic>Clostridium difficile</jats:italic>
is responsible for significant mortality and morbidity in the hospitalized elderly.
<jats:italic>C. difficile</jats:italic>
spores are infectious and are a major factor contributing to nosocomial transmission. The Spo0A response regulator is the master regulator for sporulation initiation and can influence many other cellular processes. Using the ClosTron gene knockout system, we inactivated genes encoding Spo0A and a putative sporulation-associated sensor histidine kinase in
<jats:italic>C. difficile</jats:italic>
. Inactivation of
<jats:italic>spo0A</jats:italic>
resulted in an asporogeneous phenotype, whereas inactivation of the kinase reduced
<jats:italic>C. difficle</jats:italic>
sporulation capacity by 3.5-fold, suggesting that this kinase also has a role in sporulation initiation. Furthermore, inactivation of either
<jats:italic>spo0A</jats:italic>
or the kinase resulted in a marked defect in
<jats:italic>C. difficile</jats:italic>
toxin production. Therefore, Spo0A and the signaling pathway that modulates its activity appear to be involved in regulation of toxin synthesis in
<jats:italic>C. difficile</jats:italic>
. In addition, Spo0A was directly phosphorylated by a putative sporulation-associated kinase, supporting the hypothesis that sporulation initiation in
<jats:italic>C. difficile</jats:italic>
is controlled by a two-component signal transduction system rather than a multicomponent phosphorelay. The implications of these findings for
<jats:italic>C. difficile</jats:italic>
sporulation, virulence, and transmission are discussed.
</jats:p>