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A key factor for<jats:italic>L. pneumophila<\/jats:italic>in intracellular infection is its type II protein secretion system (Lsp). In order to more completely define Lsp output, we recently performed a proteomic analysis of culture supernatants. Based upon the predictions of that analysis, we found that<jats:italic>L. pneumophila<\/jats:italic>secretes two distinct aminopeptidase activities encoded by the genes<jats:italic>lapA<\/jats:italic>and<jats:italic>lapB<\/jats:italic>. Whereas<jats:italic>lapA<\/jats:italic>conferred activity against leucine, phenylalanine, and tyrosine aminopeptides,<jats:italic>lapB<\/jats:italic>was linked to the cleavage of lysine- and arginine-containing substrates. To assess the role of secreted aminopeptidases in intracellular infection, we examined the relative abilities of<jats:italic>lapA<\/jats:italic>and<jats:italic>lapB<\/jats:italic>mutants to infect human U937 cell macrophages as well as<jats:italic>Hartmannella vermiformis<\/jats:italic>and<jats:italic>Acanthamoeba castellanii<\/jats:italic>amoebae. Although these experiments identified a dispensable role for LapA and LapB, they uncovered a previously unrecognized role for the type II-dependent ProA (MspA) metalloprotease. Whereas<jats:italic>proA<\/jats:italic>mutants were not defective for macrophage or<jats:italic>A. castellanii<\/jats:italic>infection, they (but not their complemented derivatives) were impaired for growth upon coculture with<jats:italic>H. vermiformis<\/jats:italic>. Thus, ProA represents the first type II effector implicated in an intracellular infection event. Furthermore,<jats:italic>proA<\/jats:italic>represents an<jats:italic>L. pneumophila<\/jats:italic>gene that shows differential importance among protozoan infection models, suggesting that the legionellae might have evolved some of its factors to especially target certain of their protozoan hosts.<\/jats:p>","DOI":"10.1128\/aem.01944-07","type":"journal-article","created":{"date-parts":[[2007,12,15]],"date-time":"2007-12-15T01:54:26Z","timestamp":1197683666000},"page":"753-761","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":76,"title":["The Type II Secretion System of<i>Legionella pneumophila<\/i>Elaborates Two Aminopeptidases, as Well as a Metalloprotease That Contributes to Differential Infection among Protozoan Hosts"],"prefix":"10.1128","volume":"74","author":[{"given":"Ombeline","family":"Rossier","sequence":"first","affiliation":[{"name":"Department of Microbiology-Immunology, Northwestern University Medical School, Chicago, Illinois 60611"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenny","family":"Dao","sequence":"additional","affiliation":[{"name":"Department of Microbiology-Immunology, Northwestern University Medical School, Chicago, Illinois 60611"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas P.","family":"Cianciotto","sequence":"additional","affiliation":[{"name":"Department of Microbiology-Immunology, Northwestern University Medical School, Chicago, Illinois 60611"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2836(05)80360-2"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.69.1.177-185.2001"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.4.1855-1863.2000"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1099\/00221287-148-7-2223"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M509025200"},{"key":"e_1_3_2_7_2","unstructured":"Current protocols in molecular biology 1989 vol. 1"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00956-06"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.5.2899-2909.2005"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.17.6.970-974.1983"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.16.3.452-457.1982"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-2920.2006.01229.x"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.65.11.4892-4896.1997"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M106950200"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1447"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0969-2126(00)00030-7"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1099776"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2005.09.005"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.57.4.1255-1262.1989"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.11.5188"},{"key":"e_1_3_2_21_2","first-page":"1565","volume":"132","year":"1986","unstructured":"Conlan, J. 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