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A single amino acid in E‐cadherin responsible for host specificity towards the human pathogen Listeria monocytogenes
Author(s) -
Lecuit Marc,
Dramsi Shaynoor,
Gottardi Cara,
FedorChaiken Mary,
Gumbiner Barry,
Cossart Pascale
Publication year - 1999
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/18.14.3956
Subject(s) - biology , listeria monocytogenes , pathogen , microbiology and biotechnology , host (biology) , listeria , human pathogen , foodborne pathogen , virology , genetics , bacteria
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.