Nitric oxide inhibits Shiga-toxin synthesis by enterohemorrhagic Escherichia coli
- Institut National de la Recherche Agronomique (INRA), UR454 Unité de Microbiologie, Centre de Recherches de Theix, 63122 Saint-Genès-Champanelle, France
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Edited by Roy Curtiss, Arizona State University, Tempe, AZ, and approved May 3, 2007 (received for review March 20, 2007)
Abstract
Shiga-toxin (Stx) is the cardinal virulence factor of enterohemorrhagic Escherichia coli (EHEC). The genes encoding Stx are carried by a lambdoid phage integrated in the bacterial genome and are fully expressed after a bacterial SOS response induced by DNA-damaging agents. Because nitric oxide (NO) is an essential mediator of the innate immune response of infected colonic mucosa, we aimed to determine its role in Stx production by EHEC. Here we demonstrate that chemical or cellular sources of NO inhibit spontaneous and mitomycin C-induced stx mRNA expression and Stx synthesis, without altering EHEC viability. The synthesis of stx phage is also reduced by NO. This inhibitory effect apparently occurs through the NO-mediated sensitization of EHEC because mutation of the NO sensor nitrite-sensitive repressor results in loss of NO inhibiting activity on stx expression. Thus our findings identify NO as an inhibitor of stx expressing-phage propagation and Stx release and thus as a potential protective factor limiting the development of hemolytic syndromes.
Footnotes
- *To whom correspondence should be addressed. E-mail: agobert{at}clermont.inra.fr
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Author contributions: A.P.G. designed research; M.V. performed research; T.d.S. and C.M. contributed new reagents/analytic tools; M.V., T.H., C.M., and A.P.G. analyzed data; and A.P.G. wrote the paper.
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The authors declare no conflict of interest.
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This article is a PNAS Direct Submission.
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This article contains supporting information online at www.pnas.org/cgi/content/full/0702589104/DC1.
- Abbreviations:
- EHEC,
- enterohemorrhagic Escherichia coli;
- HUS,
- hemolytic–uremic syndrome;
- Stx,
- Shiga toxin;
- iNOS,
- inducible NO synthase;
- NsrR,
- nitrite-sensitive repressor;
- NIL,
- l-N6-(1-iminoethyl)lysine.
- © 2007 by The National Academy of Sciences of the USA
