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

Human E-cadherin promotes entry of the bacterial pathogen Listeria monocyto genes into mammalian cells by interacting with internalin (InlA), a bacteri al surface protein. Here we show that mouse E-cadherin, although very simil ar 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 substitut ion 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-cad herins from several species is established, The location of this key specif icity residue in a region of E-cadherin not involved in cell-cell adhesion and the stringency of the interaction demonstrated here have important cons equences not only for the understanding of internalin function but also for the choice of the animal model to be used to study human listeriosis: mous e, albeit previously widely used, and rat appear as inappropriate animal mo dels to study all aspects of human listeriosis, as opposed to guinea-pig, w hich now stands as a small animal of choice for future in vivo studies.