Signal transduction in the protozoan host Hartmannella vermiformis upon attachment to Legionella pneumophila

Intracellular replication of the Legionnaires' disease bacterium, Legionell a pneumophila, within protozoa plays a major role in bacterial ecology and pathogenesis. Invasion of the protozoan host Hartmannella vermiformis by L. pneumophila is mediated by attachment to the Gal/GalNAc lectin receptor, w hich is similar to the beta(2), integrin transmembrane receptors of mammali an cells. Bacterial invasion is associated with induction of a protein tyro sine phosphatase (PTPase) activity in H. vermiformis that results in tyrosi ne dephosphorylation of the lectin receptor and several cytoskeletal protei ns. In this report, we show that entry oft. pneumophila into H. vermiformis is not required to induce tyrosine dephosphorylation of one of the cytoske letal proteins, paxillin. Tyrosine dephosphorylation of paxillin is mediate d at the level of bacterial attachment to the lectin receptor, and is block ed by inhibiting bacterial attachment to the lectin receptor. Attachment of t. pneumophila to the lectin receptor is not mediated by the type IV pilus, which is one of the bacterial ligands involved in attachment to protozoa. Interestingly, the lectin receptor in resting H. vermiformis is associated with several phosphorylated proteins that are dissociated upon bacterial at tachment and invasion. We show that the L. pneumophila-induced PTPase activ ity in H. vermiformis and the associated tyrosine dephosphorylation of host proteins can be mimicked by the cytoskeletal disrupting agent, cytochalasi n D. Taken together, our data indicate that attachment oft. pneumophila to the lectin receptor of H. vermiformis induces a PTPase activity, tyrosine d ephosphorylation of the lectin and cytoskeletal proteins, dissociation of t he lectin from its associated phosphorylated proteins, and most probably di sassembly of the cytoskeleton. This novel L. pneumophila-protozoa interacti on may be a bacterial strategy to invade protozoa and to be trafficked into a replicative 'niche', or to block differentiation of the protozoan host i nto a cyst in which L. pneumophila cannot replicate. (C) 2000 Editions scie ntifiques et medicales Elsevier SAS.