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J. Biol. Chem., Vol. 282, Issue 46, 33275-33283, November 16, 2007

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The Flagellar Sigma Factor FliA Regulates Adhesion and Invasion of Crohn Disease-associated Escherichia coli via a Cyclic Dimeric GMP-dependent Pathway^*

Laurent Claret¹, Sylvie Miquel, Natacha Vieille, Dmitri A. Ryjenkov^¶, Mark Gomelsky^¶, and Arlette Darfeuille-Michaud

From the Université Clermont 1, Pathogénie Bactérienne Intestinale, Institut National de la Recherche Agronomique, Unité Sous Contrat 2018 (USC INRA 2018), Clermont-Ferrand F-63001, France, the Institut Universitaire de Technologie en Génie Biologique, Aubière F-63172, France, and the ^¶Department of Molecular Biology, University of Wyoming, Laramie, Wyoming, 82071

The invasion of intestinal epithelial cells by the Crohn disease-associated adherent-invasive Escherichia coli (AIEC) strain LF82 depends on surface appendages, such as type 1 pili and flagella. The absence of flagella in the AIEC strain LF82 results in a concomitant loss of type 1 pili. Here, we show that flagellar regulators, transcriptional activator FlhD₂C₂, and sigma factor FliA are involved in the coordination of flagellar and type 1 pili synthesis. In the deletion mutants lacking these regulators, type 1 pili synthesis, adhesion, and invasion were severely decreased. FliA expressed alone in trans was sufficient to restore these defects in both the LF82-flhD and LF82-fliA mutants. We related the loss of type 1 pili to the decreased expression of the FliA-dependent yhjH gene in the LF82-fliA mutant. YhjH is an EAL domain phosphodiesterase involved in degradation of the bacterial second messenger cyclic dimeric GMP (c-di-GMP). Increased expression of either yhjH or an alternative c-di-GMP phosphodiesterase, yahA, partially restored type 1 pili synthesis, adhesion, and invasion in the LF82-fliA mutant. Deletion of the GGDEF domain diguanylate cyclase gene, yaiC, involved in c-di-GMP synthesis in the LF82-fliA mutant also partially restored these defects, whereas overexpression of the c-di-GMP receptor YcgR had the opposite effect. These findings show that in the AIEC strain LF82, FliA is a key regulatory component linking flagellar and type 1 pili synthesis and that its effect on type 1 pili is mediated, at least in part, via a c-di-GMP-dependent pathway.

Received for publication, April 2, 2007 , and in revised form, July 24, 2007.

^* This work was supported by the Ministère de la Recherche et de la Technologie (EA3844), INRA (USC-2018), grants from the Association F. Aupetit and Institut de Recherche des Maladies de l'Appareil Digestif (Laboratoire Astra France), and United States Department of Agriculture Cooperative State Research Education Extension Service Grant AD-417 via Agricultural Experimental Station Project WYO-414-07 (to M. G.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Table 1.

¹ To whom correspondence should be addressed: Pathogénie Bactérienne Intestinale, Laboratoire de bactériologie, CBRV, 28 Place Henri Dunant, 63001 Clermont-Ferrand, France. Tel.: 33-4-73-17-79-97; Fax: 33-4-73-17-83-71; E-mail: laurent.claret{at}u-clermont1.fr.