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Infection and Immunity, October 2005, p. 6912-6922, Vol. 73, No. 10
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.10.6912-6922.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

LPXTG Protein InlJ, a Newly Identified Internalin Involved in Listeria monocytogenes Virulence

Christophe Sabet,¹ Marc Lecuit,^1,2 Didier Cabanes,^1, Pascale Cossart,^1* and Hélène Bierne^1*

Unité des Interactions Bactéries-Cellules, Institut Pasteur, INSERM U604, INRA USC2020, 75724 Paris Cedex 15, France,¹ Service des Maladies infectieuses et tropicales, Université Paris 5, Hôpital Necker-Enfants maladies, 75015 Paris, France²

Received 14 March 2005/ Returned for modification 2 May 2005/ Accepted 11 June 2005

Listeria monocytogenes expresses surface proteins covalently anchored to the peptidoglycan by sortase enzymes. Inactivation of srtA attenuates Listeria virulence in mice (H. Bierne, S. K. Mazmanian, M. Trost, M. G. Pucciarelli, G. Liu, P. Dehoux, L. Jansch, F. Garcia-del Portillo, O. Schneewind, and P. Cossart, Mol. Microbiol. 43:869-881, 2002). We show here that an srtA mutant is more attenuated than an internalin mutant in orally infected guinea pigs and transgenic mice expressing human E-cadherin (hEcad mice), indicating the involvement of other SrtA substrates, LPXTG proteins, in food-borne listeriosis. Data recently generated with a listerial DNA macroarray identified two LPXTG protein-encoding genes present in the genomes of L. monocytogenes strains and absent from all other Listeria species, inlI (lmo0333) and inlJ (lmo2821). They also revealed two other LPXTG protein-encoding genes, ORF29 and ORF2568, present only in a subclass of L. monocytogenes serovars, including the epidemic serovar 4b. We report here that an inlJ deletion mutant, in contrast to inlI and ORF29 mutants, is significantly attenuated in virulence after intravenous infection of mice or oral inoculation of hEcad mice. Interestingly, a ORF2568 strain showed a slight increase in virulence. inlJ encodes a leucine-rich repeat (LRR) protein that is structurally related to the listerial invasion factor internalin. However, the consensus sequence of the InlJ LRR defines a novel subfamily of cysteine-containing LRRs in bacteria. In conclusion, this postgenomic approach identified InlJ as a new virulence factor among the proteins belonging to the internalin family in L. monocytogenes.

* Corresponding author. Mailing address: Unité des Interactions Bactéries-Cellules, Institut Pasteur, INSERM U604, INRA USC2020, 75724 Paris Cedex 15, France. Phone: 33 1 40 61 37 79. Fax: 011 33 1 45 68 87 06. E-mail: hbierne{at}pasteur.fr.

Editor: D. L. Burns

Present address: Institute for Molecular and Cell Biology, Molecular Microbiology Group, Rua do Campo Alegre, 823 4150-180 Porto, Portugal.

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