Legionella pneumophila entry gene rtxA is involved in virulence

Successful parasitism of host cells by intracellular pathogens involves adh erence, entry, survival, intracellular replication, and cell-to-cell spread . Our laboratory has been examining the role of early events, adherence and entry, in the pathogenesis of the facultative intracellular pathogen Legio nella pneumophila. Currently, the mechanisms used by L. pneumophila to gain access to the intracellular environment are not well understood. We have r ecently isolated three loci, designated enh1, enh2 and enh3, that are invol ved in the ability of L. pneumophila to enter host cells. One of the genes present in the enh1 locus, rtxA, is homologous to repeats in structural tox in genes (RTX) found in many bacterial pathogens. RTX proteins from other b acterial species are commonly cytotoxic, and some of them have been shown t o bind to beta (2) integrin receptors. In the current study, we demonstrate that the L. pneumophila rtxA gene is involved in adherence, cytotoxicity, and pore formation in addition to its role in entry. Furthermore, an rtxA m utant does not replicate as well as wild-type L. pneumophila in monocytes a nd is less virulent in mice. Thus, we conclude that the entry gene rtxA is an important virulence determinant in L. pneumophila and is likely to be cr itical for the production of Legionnaires' disease in humans.