{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T22:45:10Z","timestamp":1790635510996,"version":"4.1.0"},"reference-count":94,"publisher":"Microbiology Society","issue":"12","funder":[{"name":"NIH","award":["AI043987"],"award-info":[{"award-number":["AI043987"]}]},{"name":"NIH","award":["5K12GM088020"],"award-info":[{"award-number":["5K12GM088020"]}]},{"name":"NIH","award":["T32 AI0007476"],"award-info":[{"award-number":["T32 AI0007476"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,12,1]]},"abstract":"<jats:p>The type II protein secretion (T2S) system of <jats:italic>Legionella pneumophila<\/jats:italic> secretes over 25 proteins, including novel proteins that have no similarity to proteins of known function. T2S is also critical for the ability of <jats:italic>L. pneumophila<\/jats:italic> to grow within its natural amoebal hosts, including <jats:italic>Acanthamoeba castellanii<\/jats:italic>, <jats:italic>Hartmannella vermiformis<\/jats:italic> and <jats:italic>Naegleria lovaniensis<\/jats:italic>. Thus, T2S has an important role in the natural history of legionnaires\u2019 disease. Our previous work demonstrated that the novel T2S substrate NttA promotes intracellular infection of <jats:italic>A. castellanii<\/jats:italic>, whereas the secreted RNase SrnA, acyltransferase PlaC, and metalloprotease ProA all promote infection of <jats:italic>H. vermiformis<\/jats:italic> and <jats:italic>N. lovaniensis<\/jats:italic>. In this study, we determined that another novel T2S substrate that is specific to <jats:italic>Legionella<\/jats:italic>, designated NttC, is unique in being required for intracellular infection of <jats:italic>H. vermiformis<\/jats:italic> but not for infection of <jats:italic>N. lovaniensis<\/jats:italic> or <jats:italic>A. castellanii<\/jats:italic>. Expanding our repertoire of amoebal hosts, we determined that <jats:italic>Willaertia magna<\/jats:italic> is susceptible to infection by <jats:italic>L. pneumophila<\/jats:italic> strains 130b, Philadelphia-1 and Paris. Furthermore, T2S and, more specifically, NttA, NttC and PlaC were required for infection of <jats:italic>W. magna<\/jats:italic>. Taken together, these data demonstrate that the T2S system of <jats:italic>L. pneumophila<\/jats:italic> is critical for infection of at least four types of aquatic amoebae and that the importance of the individual T2S substrates varies in a host cell-specific fashion. Finally, it is now clear that novel T2S-dependent proteins that are specific to the genus <jats:italic>Legionella<\/jats:italic> are particularly important for <jats:italic>L. pneumophila<\/jats:italic> infection of key, environmental hosts.<\/jats:p>","DOI":"10.1099\/mic.0.082750-0","type":"journal-article","created":{"date-parts":[[2014,9,25]],"date-time":"2014-09-25T05:45:10Z","timestamp":1411623910000},"page":"2732-2744","source":"Crossref","is-referenced-by-count":39,"title":["The novel Legionella pneumophila type II secretion substrate NttC contributes to infection of amoebae Hartmannella vermiformis and Willaertia magna"],"prefix":"10.1099","volume":"160","author":[{"given":"Jessica Y.","family":"Tyson","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Northwestern University Medical School, Chicago, IL 60611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paloma","family":"Vargas","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Northwestern University Medical School, Chicago, IL 60611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas P.","family":"Cianciotto","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Northwestern University Medical School, Chicago, IL 60611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"345","reference":[{"key":"r1","doi-asserted-by":"crossref","first-page":"2360","DOI":"10.1128\/AEM.57.8.2360-2367.1991","article-title":"Risk factors for contamination of domestic hot water systems by legionellae","volume":"57","author":"Alary","year":"1991","journal-title":"Appl Environ Microbiol"},{"key":"r2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.06626-11"},{"key":"r3","doi-asserted-by":"publisher","DOI":"10.1017\/S0022172400060174"},{"key":"r4","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.4.1855-1863.2000"},{"key":"r5","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.69.1.177-185.2001"},{"key":"r6","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.5.2899-2909.2005"},{"key":"r7","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1128\/AEM.51.2.422-424.1986","article-title":"Isolation of protozoa from water associated with a legionellosis outbreak and demonstration of intracellular multiplication of Legionella pneumophila","volume":"51","author":"Barbaree","year":"1986","journal-title":"Appl Environ Microbiol"},{"key":"r8","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1128\/AEM.64.1.279-286.1998","article-title":"Production of respirable vesicles containing live Legionella pneumophila cells by two Acanthamoeba spp.","volume":"64","author":"Berk","year":"1998","journal-title":"Appl Environ Microbiol"},{"key":"r9","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1990.03440210074036"},{"key":"r10","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-90-4-656"},{"key":"r11","doi-asserted-by":"publisher","DOI":"10.1099\/00207713-35-1-50"},{"key":"r12","doi-asserted-by":"crossref","first-page":"5330","DOI":"10.1128\/IAI.65.12.5330-5333.1997","article-title":"The role of Legionella pneumophila-infected Hartmannella vermiformis as an infectious particle in a murine model of Legionnaire\u2019s disease","volume":"65","author":"Brieland","year":"1997","journal-title":"Infect Immun"},{"key":"r13","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijmm.2013.07.003"},{"key":"r14","doi-asserted-by":"publisher","DOI":"10.1111\/j.1472-765X.2011.03094.x"},{"key":"r15","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1128\/AEM.47.2.369-373.1984","article-title":"Legionella sainthelensi: a new species of Legionella isolated from water near Mt. 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