Listeria monocytogenes internalin and E-cadherin: from structure to pathogenesis.
Many bacterial pathogens that invade non-phagocytic cells first interact with host cell surface receptors. Adhesion to the host cell is followed by the activation of specific host signalling pathways that mediate bacterial internalization. The food-borne Gram-positive bacterium Listeria monocytogenes makes use of two surface proteins, internalin (InlA) and InlB to engage in a species-specific manner the adhesion molecule E-cadherin and the hepatocyte growth factor receptor Met, respectively, to induce its internalization. After entry, Listeria has the capacity to spread from cell to cell and disseminate to its target organs after breaching the intestinal, blood-brain and placental barriers in human. InlA but not InlB is critical for the crossing of the intestinal barrier, whereas the conjugated action of both InlA and InlB mediates the crossing of the placental barrier. Here we review the InlA-E-cadherin interaction, the signalling downstream of this interaction, the molecular mechanisms involved in bacterial internalization and the role of InlA-E-cadherin interaction in the breaching of host barriers and the progression to listeriosis. Together, this review illustrates how in vitro data were validated by epidemiological approaches and in vivo studies using both natural hosts and genetically engineered animal models, thereby elucidating key issues of listeriosis pathophysiology.
Bonazzi
Matteo
M
Unité des Interactions Bactéries-Cellules, Institut Pasteur, Paris, France.
Lecuit
Marc
M
Cossart
Pascale
P
D000818:Animals; D001422:Bacterial Adhesion / Q000502:physiology; D001426:Bacterial Proteins / Q000378:metabolism / Q000502:physiology*; D015820:Cadherins / Q000378:metabolism / Q000502:physiology*; D004705:Endocytosis; D006801:Humans; D008089:Listeria monocytogenes / Q000378:metabolism / Q000472:pathogenicity*; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008954:Models, Biological; D010587:Phagocytosis; D015398:Signal Transduction; D013045:Species Specificity; D037521:Virulence Factors / Q000378:metabolism / Q000502:physiology*
D001426:Bacterial Proteins; D015820:Cadherins; D008565:Membrane Proteins; D037521:Virulence Factors