A single amino acid in E-cadherin responsible for host specificity towards the human pathogen Listeria monocytogenes

Marc Lecuit, Shaynoor Dramsi, Cara Gottardi, Mary Fedor-Chaiken, Barry Gumbiner, Pascale Cossart*

*Corresponding author for this work

Research output: Contribution to journalArticle

338 Scopus citations

Abstract

Human E-cadherin promotes entry of the bacterial pathogen Listeria monocytogenes into mammalian cells by interacting with internalin (InlA), a bacterial surface protein. Here we show that mouse E-cadherin, although very similar to human E-cadherin (85% identity), is not a receptor for internalin. By a series of domain-swapping and mutagenesis experiments, we identify Pro16 of E-cadherin as a residue critical for specificity: a Pro → Glu substitution in human E-cadherin totally abrogates interaction, whereas a Glu → Pro substitution in mouse E-cadherin results in a complete gain of function. A correlation between cell permissivity and the nature of residue 16 in E-cadherins from several species is established. The location of this key specificity residue in a region of E-cadherin not involved in cell-cell adhesion and the stringency of the interaction demonstrated here have important consequences not only for the understanding of internalin function but also for the choice of the animal model to be used to study human listeriosis: mouse, albeit previously widely used, and rat appear as inappropriate animal models to study all aspects of human listeriosis, as opposed to guinea-pig, which now stands as a small animal of choice for future in vivo studies.

Original languageEnglish (US)
Pages (from-to)3956-3963
Number of pages8
JournalEMBO Journal
Volume18
Issue number14
DOIs
StatePublished - Jul 15 1999

Keywords

  • E-cadherin
  • Internalin
  • Invasion
  • Listeria
  • Specificity

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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