{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T06:18:09Z","timestamp":1791267489620,"version":"4.1.0"},"reference-count":57,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2008,7,1]],"date-time":"2008-07-01T00:00:00Z","timestamp":1214870400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2008,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Previously, we identified\n            <jats:italic>ladC<\/jats:italic>\n            in a cohort of genes that were present in\n            <jats:italic>Legionella pneumophila<\/jats:italic>\n            but absent in other\n            <jats:italic>Legionella<\/jats:italic>\n            species. Here we constructed a\n            <jats:italic>ladC<\/jats:italic>\n            mutant of\n            <jats:italic>L. pneumophila<\/jats:italic>\n            and assessed its ability to replicate in mammalian cell lines and\n            <jats:italic>Acanthamoeba castellanii<\/jats:italic>\n            . The\n            <jats:italic>ladC<\/jats:italic>\n            mutant was recovered in significantly lower numbers than wild-type\n            <jats:italic>L. pneumophila<\/jats:italic>\n            at early time points, which was reversed upon transcomplementation with\n            <jats:italic>ladC<\/jats:italic>\n            but not\n            <jats:italic>ladC<\/jats:italic>\n            <jats:sub>N430A\/R434A<\/jats:sub>\n            , encoding a putative catalytically inactive derivative of the protein. In fact, complementation of\n            <jats:italic>ladC<\/jats:italic>\n            ::Km with\n            <jats:italic>ladC<\/jats:italic>\n            <jats:sub>N430A\/R434A<\/jats:sub>\n            resulted in a severe replication defect within human and amoeba cell models of infection, which did not follow a typical dominant negative phenotype. Using differential immunofluorescence staining to distinguish adherent from intracellular bacteria, we found that the\n            <jats:italic>ladC<\/jats:italic>\n            mutant exhibited a 10-fold reduction in adherence to THP-1 macrophages but no difference in uptake by THP-1 cells. When tested in vivo in A\/J mice, the competitive index of the\n            <jats:italic>ladC<\/jats:italic>\n            mutant dropped fivefold over 72 h, indicating a significant attenuation compared to wild-type\n            <jats:italic>L. pneumophila<\/jats:italic>\n            . Although localization of LadC to the bacterial inner membrane suggested that the protein may be involved in signaling pathways that regulate virulence gene expression, microarray analysis indicated that\n            <jats:italic>ladC<\/jats:italic>\n            does not influence the transcriptional profile of\n            <jats:italic>L. pneumophila<\/jats:italic>\n            in vitro or during\n            <jats:italic>A. castellanii<\/jats:italic>\n            infection. Although the mechanism by which LadC modulates the initial interaction between the bacterium and host cell remains unclear, we have established that LadC plays an important role in\n            <jats:italic>L. pneumophila<\/jats:italic>\n            infection.\n          <\/jats:p>","DOI":"10.1128\/iai.00209-08","type":"journal-article","created":{"date-parts":[[2008,4,22]],"date-time":"2008-04-22T02:42:26Z","timestamp":1208832146000},"page":"3075-3085","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":35,"title":["Significant Role for\n            <i>ladC<\/i>\n            in Initiation of\n            <i>Legionella pneumophila<\/i>\n            Infection"],"prefix":"10.1128","volume":"76","author":[{"given":"Hayley J.","family":"Newton","sequence":"first","affiliation":[{"name":"Australian Bacterial Pathogenesis Program, Department of Microbiology, Monash University, Victoria 3800, Australia"},{"name":"Department of Microbiology and Immunology, University of Melbourne, Victoria 3010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiona M.","family":"Sansom","sequence":"additional","affiliation":[{"name":"Australian Bacterial Pathogenesis Program, Department of Microbiology, Monash University, Victoria 3800, Australia"},{"name":"Department of Microbiology and Immunology, University of Melbourne, Victoria 3010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenny","family":"Dao","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Northwestern University Medical School, Chicago, Illinois 60611"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christel","family":"Cazalet","sequence":"additional","affiliation":[{"name":"Biologie des Bacte\u0301ries Intracellulaires, Institut Pasteur, and CNRS URA 2171, Paris Cedex 15, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holger","family":"Bruggemann","sequence":"additional","affiliation":[{"name":"Biologie des Bacte\u0301ries Intracellulaires, Institut Pasteur, and CNRS URA 2171, Paris Cedex 15, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiane","family":"Albert-Weissenberger","sequence":"additional","affiliation":[{"name":"Biologie des Bacte\u0301ries Intracellulaires, Institut Pasteur, and CNRS URA 2171, Paris Cedex 15, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Buchrieser","sequence":"additional","affiliation":[{"name":"Biologie des Bacte\u0301ries Intracellulaires, Institut Pasteur, and CNRS URA 2171, Paris Cedex 15, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas P.","family":"Cianciotto","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Northwestern University Medical School, Chicago, Illinois 60611"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth L.","family":"Hartland","sequence":"additional","affiliation":[{"name":"Australian Bacterial Pathogenesis Program, Department of Microbiology, Monash University, Victoria 3800, Australia"},{"name":"Department of Microbiology and Immunology, University of Melbourne, Victoria 3010, 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