{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T02:06:40Z","timestamp":1792721200417,"version":"4.5.0"},"reference-count":45,"publisher":"National Academy of Sciences","issue":"50","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2010,12,14]]},"abstract":"\n Coxiella burnetii<\/jats:italic>\n is an obligate intracellular bacterial pathogen responsible for acute and chronic Q fever. This bacterium harbors a type IV secretion system (T4SS) highly similar to the Dot\/Icm of\n Legionella pneumophila<\/jats:italic>\n that is believed to be essential for its infectivity. Protein substrates of the\n Coxiella<\/jats:italic>\n T4SS are predicted to facilitate the biogenesis of a phagosome permissive for its intracellular growth. However, due to the lack of genetic systems, protein transfer by the\n C. burnetii<\/jats:italic>\n Dot\/Icm has not been demonstrated. In this study, we report the identification of 32 substrates of the\n C. burnetii<\/jats:italic>\n Dot\/Icm system using a fluorescence-based \u03b2-lactamase (TEM1) translocation assay as well as the calmodulin-dependent adenylate cyclase (CyaA) assay in the surrogate host\n L. pneumophila<\/jats:italic>\n . Notably, 26 identified T4SS substrates are hypothetical proteins without predicted function. Candidate secretion substrates were obtained by using (\n i<\/jats:italic>\n ) a genetic screen to identify\n C. burnetii<\/jats:italic>\n proteins interacting with DotF, a component of the T4SS, and (\n ii<\/jats:italic>\n ) bioinformatic approaches to retrieve candidate genes that harbor characteristics associated with previously reported substrates of the Dot\/Icm system from both\n C. burnetii<\/jats:italic>\n and\n L. pneumophila<\/jats:italic>\n . Moreover, we have developed a shuttle plasmid that allows the expression of recombinant proteins in\n C. burnetii<\/jats:italic>\n as TEM fusion products. Using this system, we demonstrated that a Dot\/Icm substrate identified with\n L. pneumophila<\/jats:italic>\n was also translocated by\n C. burnetii<\/jats:italic>\n in a process that requires its C terminus, providing direct genetic evidence of a functional T4SS in\n C. burnetii<\/jats:italic>\n .\n <\/jats:p>","DOI":"10.1073\/pnas.1010485107","type":"journal-article","created":{"date-parts":[[2010,11,23]],"date-time":"2010-11-23T22:42:32Z","timestamp":1290552152000},"page":"21755-21760","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":191,"title":["Large-scale identification and translocation of type IV secretion substrates by\n Coxiella burnetii<\/i>"],"prefix":"10.1073","volume":"107","author":[{"given":"Chen","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Microbial and Molecular Pathogenesis, Texas A&M Health Science Center, College Station, TX 77843; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simran","family":"Banga","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Purdue University, West Lafayette, IN 47907"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja","family":"Mertens","sequence":"additional","affiliation":[{"name":"Department of Microbial and Molecular Pathogenesis, Texas A&M Health Science Center, College Station, TX 77843; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary M.","family":"Weber","sequence":"additional","affiliation":[{"name":"Department of Microbial and Molecular Pathogenesis, Texas A&M Health Science Center, College Station, TX 77843; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivana","family":"Gorbaslieva","sequence":"additional","affiliation":[{"name":"Department of Microbial and Molecular Pathogenesis, Texas A&M Health Science Center, College Station, TX 77843; 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