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Our laboratory has been examining the role of early events, adherence and entry, in the pathogenesis of the facultative intracellular pathogen<jats:italic>Legionella pneumophila<\/jats:italic>. Currently, the mechanisms used by<jats:italic>L. pneumophila<\/jats:italic>to gain access to the intracellular environment are not well understood. We have recently isolated three loci, designated<jats:italic>enh1<\/jats:italic>,<jats:italic>enh2<\/jats:italic>, and<jats:italic>enh3<\/jats:italic>, that are involved in the ability of<jats:italic>L. pneumophila<\/jats:italic>to enter host cells. One of the genes present in the<jats:italic>enh1<\/jats:italic>locus,<jats:italic>rtxA<\/jats:italic>, 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 \u03b2<jats:sub>2<\/jats:sub>integrin receptors. In the current study, we demonstrate that the<jats:italic>L. pneumophila rtxA<\/jats:italic>gene is involved in adherence, cytotoxicity, and pore formation in addition to its role in entry. Furthermore, an<jats:italic>rtxA<\/jats:italic>mutant does not replicate as well as wild-type<jats:italic>L. pneumophila<\/jats:italic>in monocytes and is less virulent in mice. Thus, we conclude that the entry gene<jats:italic>rtxA<\/jats:italic>is an important virulence determinant in<jats:italic>L. pneumophila<\/jats:italic>and is likely to be critical for the production of Legionnaires' disease in humans.<\/jats:p>","DOI":"10.1128\/iai.69.1.508-517.2001","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T09:58:18Z","timestamp":1027763898000},"page":"508-517","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":110,"title":["<i>Legionella pneumophila<\/i>Entry Gene<i>rtxA<\/i>Is Involved in Virulence"],"prefix":"10.1128","volume":"69","author":[{"given":"Suat L. 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