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The Oxidoreductase DsbA Plays a Key Role in the Ability of the Crohn's Disease-Associated Adherent-Invasive Escherichia coli Strain LF82 To Resist Macrophage Killing

Marie-Agnès Bringer,^1,2, Nathalie Rolhion,^1,2, Anne-Lise Glasser,^1,2 and Arlette Darfeuille-Michaud^1,2*

Université Clermont I, Pathogénie Bactérienne Intestinale, USC INRA 2018, F-63000 Clermont-Fd,¹ Institut Universitaire de Technologie en Génie Biologique, F-63172 Aubière, France²

Received 12 February 2007/ Accepted 5 April 2007

Adherent-invasive Escherichia coli (AIEC) isolated from Crohn's disease patients is able to adhere to and invade intestinal epithelial cells and to replicate in mature phagolysosomes within macrophages. Here, we show that the dsbA gene, encoding a periplasmic oxidoreductase, was required for AIEC strain LF82 to adhere to intestinal epithelial cells and to survive within macrophages. The LF82-dsbA mutant did not express flagella and, probably as a consequence of this, did not express type 1 pili. The role of DsbA in adhesion is restricted to the loss of flagella and type 1 pili, as forced contact between bacteria and cells and induced expression of type 1 pili restored the wild-type phenotype. In contrast, the dsbA gene is essential for AIEC LF82 bacteria to survive within macrophages, irrespective of the loss of flagella and type 1 pilus expression, and the survival ability of LF82-dsbA was as low as that of the nonpathogenic E. coli K-12, which was efficiently killed by macrophages. We also provide evidence that the dsbA gene is needed for LF82 bacteria to grow and survive in an acidic and nutrient-poor medium that partly mimics the harsh environment of the phagocytic vacuole. In addition, under such stress conditions dsbA transcription is highly up-regulated. Finally, the CpxRA signaling pathway does not play a role in regulation of dsbA expression in AIEC LF82 bacteria under conditions similar to those of mature phagolysosomes.

Published ahead of print on 20 April 2007.

M.-A.B. and N.R. contributed equally to this work.

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