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Infection and Immunity, January 2003, p. 474-482, Vol. 71, No. 1
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.1.474-482.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Identification of LpeA, a PsaA-Like Membrane Protein That Promotes Cell Entry by Listeria monocytogenes

INSERM U570, Faculté de Médecine Necker-Enfants Malades, 75730 Paris cedex 15, France

Received 5 July 2002/ Returned for modification 12 September 2002/ Accepted 22 October 2002

The intracellular life of Listeria monocytogenes starts by a complex process of entry involving several bacterial ligands and eukaryotic receptors. In this work, we identified in silico from the sequence of the genome of L. monocytogenes a previously unknown gene designated lpeA (for lipoprotein promoting entry) encoding a 35-kDa protein homologous to PsaA, a lipoprotein belonging to the LraI family and implicated in the cell adherence of Streptococcus pneumoniae and related species. By constructing a mutant of L. monocytogenes in which lpeA is deleted (lpeA mutant), we show that the PsaA-like protein LpeA is not involved in bacterial adherence but is required for entry of L. monocytogenes in eukaryotic cells. In contrast to wild-type bacteria, mutant bacteria failed to invade the epithelial Caco-2 and hepatocyte TIB73 cell lines, as confirmed by confocal microscopy. The mutant bacteria rapidly penetrated in mouse bone marrow-derived macrophages. Surprisingly, lpeA mutant bacteria survive better in macrophages than do wild-type bacteria. This was correlated with a weak exacerbation of virulence of the lpeA mutant in the mouse. LpeA is therefore a novel invasin favoring the entry of L. monocytogenes into nonprofessional phagocytes but not its invasion of macrophages. This is the first report of a lipoprotein promoting cell invasion of an intracellular pathogen.

Editor: J. D. Clements

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