{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T14:17:08Z","timestamp":1793888228090,"version":"4.8.0"},"reference-count":42,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2011,4,1]],"date-time":"2011-04-01T00:00:00Z","timestamp":1301616000000},"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":[[2011,4]]},"abstract":"ABSTRACT<\/jats:title>\n \n The\n Burkholderia pseudomallei<\/jats:italic>\n K96243<\/jats:ext-link>\n genome encodes six type VI secretion systems (T6SSs), but little is known about the role of these systems in the biology of\n B. pseudomallei<\/jats:italic>\n . In this study, we purified recombinant Hcp proteins from each T6SS and tested them as vaccine candidates in the BALB\/c mouse model of melioidosis. Recombinant Hcp2 protected 80% of mice against a lethal challenge with\n K96243<\/jats:ext-link>\n , while recombinant Hcp1, Hcp3, and Hcp6 protected 50% of mice against challenge. Hcp6 was the only Hcp constitutively produced by\n B. pseudomallei in vitro<\/jats:italic>\n ; however, it was not exported to the extracellular milieu. Hcp1, on the other hand, was produced and exported\n in vitro<\/jats:italic>\n when the VirAG two-component regulatory system was overexpressed in\n trans<\/jats:italic>\n . We also constructed six\n hcp<\/jats:italic>\n deletion mutants (\n \u0394hcp1<\/jats:italic>\n through\n \u0394hcp6<\/jats:italic>\n ) and tested them for virulence in the Syrian hamster model of infection. The 50% lethal doses (LD\n 50<\/jats:sub>\n s) for the\n \u0394hcp2<\/jats:italic>\n through\n \u0394hcp6<\/jats:italic>\n mutants were indistinguishable from\n K96243<\/jats:ext-link>\n (<10 bacteria), but the LD\n 50<\/jats:sub>\n for the\n \u0394hcp1<\/jats:italic>\n mutant was >10\n 3<\/jats:sup>\n bacteria. The\n hcp1<\/jats:italic>\n deletion mutant also exhibited a growth defect in RAW 264.7 macrophages and was unable to form multinucleated giant cells in this cell line. Unlike\n K96243<\/jats:ext-link>\n , the\n \u0394hcp1<\/jats:italic>\n mutant was only weakly cytotoxic to RAW 264.7 macrophages 18 h after infection. The results suggest that the cluster 1 T6SS is essential for virulence and plays an important role in the intracellular lifestyle of\n B. pseudomallei<\/jats:italic>\n .\n <\/jats:p>","DOI":"10.1128\/iai.01218-10","type":"journal-article","created":{"date-parts":[[2011,2,8]],"date-time":"2011-02-08T00:24:35Z","timestamp":1297124675000},"page":"1512-1525","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":258,"title":["The Cluster 1 Type VI Secretion System Is a Major Virulence Determinant in\n Burkholderia pseudomallei<\/i>"],"prefix":"10.1128","volume":"79","author":[{"given":"Mary N.","family":"Burtnick","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, University of South Alabama, Mobile, Alabama 36688"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul J.","family":"Brett","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of South Alabama, Mobile, Alabama 36688"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah V.","family":"Harding","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Defence Science and Technology Laboratory, Porton Down, Salisbury SP4 0JQ, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah A.","family":"Ngugi","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Defence Science and Technology Laboratory, Porton Down, Salisbury SP4 0JQ, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilson J.","family":"Ribot","sequence":"additional","affiliation":[{"name":"Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland 21702"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Narisara","family":"Chantratita","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology and Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo","family":"Scorpio","sequence":"additional","affiliation":[{"name":"National Biodefense Analysis and Countermeasures Center, Frederick, Maryland 21702"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy S.","family":"Milne","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Defence Science and Technology Laboratory, Porton Down, Salisbury SP4 0JQ, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel E.","family":"Dean","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Defence Science and Technology Laboratory, Porton Down, Salisbury SP4 0JQ, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David L.","family":"Fritz","sequence":"additional","affiliation":[{"name":"Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland 21702"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon J.","family":"Peacock","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne L.","family":"Prior","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Defence Science and Technology Laboratory, Porton Down, Salisbury SP4 0JQ, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy P.","family":"Atkins","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Defence Science and Technology Laboratory, Porton Down, Salisbury SP4 0JQ, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"DeShazer","sequence":"additional","affiliation":[{"name":"Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland 21702"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.32.5.500"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00370-10"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2006.00807.x"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2010.07171.x"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-10-104"},{"key":"e_1_3_2_7_2","first-page":"487","volume":"10","year":"2008","unstructured":"Brett, P. 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