Legionella pneumophilaEntry GenertxAIs Involved in Virulence

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Abstract
Successful parasitism of host cells by intracellular pathogens involves adherence, 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 pathogenLegionella pneumophila. Currently, the mechanisms used byL. pneumophilato gain access to the intracellular environment are not well understood. We have recently isolated three loci, designatedenh1,enh2, andenh3, that are involved in the ability ofL. pneumophilato enter host cells. One of the genes present in theenh1locus,rtxA, is homologous to repeats in structural toxin genes (RTX) found in many bacterial pathogens. RTX proteins from other bacterial species are commonly cytotoxic, and some of them have been shown to bind to β2integrin receptors. In the current study, we demonstrate that theL. pneumophila rtxAgene is involved in adherence, cytotoxicity, and pore formation in addition to its role in entry. Furthermore, anrtxAmutant does not replicate as well as wild-typeL. pneumophilain monocytes and is less virulent in mice. Thus, we conclude that the entry genertxAis an important virulence determinant inL. pneumophilaand is likely to be critical for the production of Legionnaires' disease in humans.