{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T23:41:41Z","timestamp":1777419701256,"version":"3.51.4"},"reference-count":33,"publisher":"Microbiology Society","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2004,8,1]]},"abstract":"<jats:p>Melioidosis is a severe infectious disease of animals and humans caused by the Gram-negative intracellular pathogen <jats:italic>Burkholderia pseudomallei<\/jats:italic>. An Inv\/Mxi-Spa-like type III protein secretion apparatus, encoded by the <jats:italic>B. pseudomallei bsa<\/jats:italic> locus, facilitates bacterial invasion of epithelial cells, escape from endocytic vesicles and intracellular survival. This study investigated the role of the Bsa type III secretion system in the pathogenesis of melioidosis in murine models. <jats:italic>B. pseudomallei bipD<\/jats:italic> mutants, lacking a component of the translocation apparatus, were found to be significantly attenuated following intraperitoneal or intranasal challenge of BALB\/c mice. Furthermore, a <jats:italic>bipD<\/jats:italic> mutant was attenuated in C57BL\/6 IL-12 p40<jats:sup>\u2212\/\u2212<\/jats:sup> mice, which are highly susceptible to <jats:italic>B. pseudomallei<\/jats:italic> infection. Mutation of <jats:italic>bipD<\/jats:italic> impaired bacterial replication in the liver and spleen of BALB\/c mice in the early stages of infection. <jats:italic>B. pseudomallei<\/jats:italic> mutants lacking either the type III secreted guanine nucleotide exchange factor BopE or the putative effectors BopA or BopB exhibited varying degrees of attenuation, with mutations in <jats:italic>bopA<\/jats:italic> and <jats:italic>bopB<\/jats:italic> causing a significant delay in median time to death. This indicates that <jats:italic>bsa<\/jats:italic>-encoded type III secreted proteins may act in concert to determine the outcome of <jats:italic>B. pseudomallei<\/jats:italic> infection in mice. Mice inoculated with the <jats:italic>B. pseudomallei bipD<\/jats:italic> mutant were partially protected against subsequent challenge with wild-type <jats:italic>B. pseudomallei<\/jats:italic>. However, immunization of mice with purified BipD protein was not protective.<\/jats:p>","DOI":"10.1099\/mic.0.27146-0","type":"journal-article","created":{"date-parts":[[2004,8,2]],"date-time":"2004-08-02T23:17:26Z","timestamp":1091488646000},"page":"2669-2676","source":"Crossref","is-referenced-by-count":153,"title":["Attenuated virulence and protective efficacy of a Burkholderia pseudomallei bsa type III secretion mutant in murine models of melioidosis"],"prefix":"10.1099","volume":"150","author":[{"given":"Mark P.","family":"Stevens","sequence":"first","affiliation":[{"name":"Division of Microbiology, Institute for Animal Health, Compton Laboratory, Berkshire RG20 7NN, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashraful","family":"Haque","sequence":"additional","affiliation":[{"name":"Immunology Unit, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel St, London WC1E 7HT, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy","family":"Atkins","sequence":"additional","affiliation":[{"name":"Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire SP4 0JQ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jim","family":"Hill","sequence":"additional","affiliation":[{"name":"Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire SP4 0JQ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael W.","family":"Wood","sequence":"additional","affiliation":[{"name":"Division of Microbiology, Institute for Animal Health, Compton Laboratory, Berkshire RG20 7NN, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Easton","sequence":"additional","affiliation":[{"name":"Immunology Unit, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel St, London WC1E 7HT, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelle","family":"Nelson","sequence":"additional","affiliation":[{"name":"Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire SP4 0JQ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cindy","family":"Underwood-Fowler","sequence":"additional","affiliation":[{"name":"Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire SP4 0JQ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard W.","family":"Titball","sequence":"additional","affiliation":[{"name":"Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire SP4 0JQ, UK"},{"name":"Immunology Unit, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel St, London WC1E 7HT, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregory J.","family":"Bancroft","sequence":"additional","affiliation":[{"name":"Immunology Unit, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel St, London WC1E 7HT, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edouard E.","family":"Galyov","sequence":"additional","affiliation":[{"name":"Division of Microbiology, Institute for Animal Health, Compton Laboratory, Berkshire RG20 7NN, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"345","reference":[{"key":"R1","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1111\/j.1365-2958.1992.tb00885.x","article-title":"icsB: a Shigella flexneri virulence gene necessary for the lysis of protrusions during intercellular spread","volume":"6","author":"Allaoui","year":"1992","journal-title":"Mol Microbiol"},{"key":"R2","doi-asserted-by":"crossref","first-page":"5290","DOI":"10.1128\/IAI.70.9.5290-5294.2002","article-title":"A mutant of Burkholderia pseudomallei, auxotrophic in the branched chain amino acid biosynthetic pathway, is attenuated and protective in a murine model of melioidosis","volume":"70","author":"Atkins","year":"2002a","journal-title":"Infect Immun"},{"key":"R3","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1099\/0022-1317-51-7-539","article-title":"Characterisation of an acapsular mutant of Burkholderia pseudomallei identified by signature tagged mutagenesis","volume":"51","author":"Atkins","year":"2002b","journal-title":"J Med Microbiol"},{"key":"R4","doi-asserted-by":"crossref","first-page":"3197","DOI":"10.1099\/00221287-147-12-3197","article-title":"A second type III secretion system in Burkholderia pseudomallei: who is the real culprit?","volume":"147","author":"Attree","year":"2001","journal-title":"Microbiology"},{"key":"R5","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1128\/IAI.69.1.367-377.2001","article-title":"Salmonella pathogenicity island 2 influences both systemic salmonellosis and Salmonella-induced enteritis in calves","volume":"69","author":"Bispham","year":"2001","journal-title":"Infect Immun"},{"key":"R6","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1093\/infdis\/168.5.1181","article-title":"Relapse in melioidosis: incidence and risk factors","volume":"168","author":"Chaowagul","year":"1993","journal-title":"J Infect Dis"},{"key":"R7","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1046\/j.1365-2958.1997.3781740.x","article-title":"The invasion-associated type III system of Salmonella typhimurium directs the translocation of Sip proteins into the host cell","volume":"24","author":"Collazo","year":"1997","journal-title":"Mol Microbiol"},{"key":"R8","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1146\/annurev.micro.54.1.735","article-title":"Assembly and function of type III secretion systems","volume":"54","author":"Cornelis","year":"2000","journal-title":"Annu Rev Microbiol"},{"key":"R9","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1146\/annurev.cellbio.17.1.53","article-title":"Salmonella interactions with host cells: type III secretion at work","volume":"17","author":"Gala\u0301n","year":"2001","journal-title":"Annu Rev Cell Dev Biol"},{"key":"R10","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1128\/MMBR.62.2.379-433.1998","article-title":"Type III protein secretion systems in bacterial pathogens of animals and plants","volume":"62","author":"Hueck","year":"1998","journal-title":"Microbiol Mol Biol Rev"},{"key":"R11","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1128\/IAI.64.3.782-790.1996","article-title":"Intracellular survival of Burkholderia pseudomallei","volume":"64","author":"Jones","year":"1996","journal-title":"Infect Immun"},{"key":"R12","doi-asserted-by":"crossref","first-page":"7078","DOI":"10.1128\/JB.177.24.7078-7085.1995","article-title":"Identification of two targets of the type III protein secretion system encoded by the inv and spa loci of Salmonella typhimurium that have homology to the Shigella IpaD and IpaA proteins","volume":"177","author":"Kaniga","year":"1995","journal-title":"J Bacteriol"},{"key":"R13","doi-asserted-by":"crossref","first-page":"5377","DOI":"10.1128\/IAI.68.9.5377-5384.2000","article-title":"Burkholderia pseudomallei induces cell fusion and actin-associated membrane protrusion: a possible mechanism of cell-to-cell spreading","volume":"68","author":"Kespichayawattana","year":"2000","journal-title":"Infect Immun"},{"key":"R14","doi-asserted-by":"crossref","first-page":"2854","DOI":"10.1128\/IAI.63.8.2854-2858.1995","article-title":"Active immunisation with recombinant V antigen from Yersinia pestis protects mice against plague","volume":"63","author":"Leary","year":"1995","journal-title":"Infect Immun"},{"key":"R15","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.1128\/JB.178.5.1310-1319.1996","article-title":"Flagellin A is essential for the virulence of Vibrio anguillarum","volume":"178","author":"Milton","year":"1996","journal-title":"J Bacteriol"},{"key":"R16","doi-asserted-by":"crossref","first-page":"14057","DOI":"10.1073\/pnas.95.24.14057","article-title":"SopB, a protein required for virulence of Salmonella dublin, is an inositol phosphatase","volume":"95","author":"Norris","year":"1998","journal-title":"Proc Natl Acad Sci U S A"},{"key":"R17","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1099\/00222615-31-2-109","article-title":"Survival of Pseudomonas pseudomallei in human phagocytes","volume":"31","author":"Pruksachartvuthi","year":"1990","journal-title":"J Med Microbiol"},{"key":"R18","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1099\/0022-1317-51-5-374","article-title":"Distribution of type III secretion gene clusters in Burkholderia pseudomallei, B. thailandensis and B. mallei","volume":"51","author":"Rainbow","year":"2002","journal-title":"J Med Microbiol"},{"key":"R19","first-page":"493","article-title":"A simple method for estimating fifty percent endpoints","volume":"27","author":"Reed","year":"1938","journal-title":"Am J Hyg"},{"key":"R20","first-page":"3","article-title":"Rupture, invasion and inflammatory destruction of the intestinal barrier by Shigella, making sense of prokaryote-eukaryote cross-talks","volume":"25","author":"Sansonetti","year":"2001","journal-title":"FEMS Microbiol Rev"},{"key":"R21","doi-asserted-by":"crossref","first-page":"3593","DOI":"10.1128\/IAI.67.7.3593-3600.1999","article-title":"Obligatory role of gamma interferon for host survival in a murine model of infection with Burkholderia pseudomallei","volume":"67","author":"Santanirand","year":"1999","journal-title":"Infect Immun"},{"key":"R22","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1038\/7391","article-title":"Active and passive immunisation with the Pseudomonas V antigen protects against type III intoxication and lung injury","volume":"5","author":"Sawa","year":"1999","journal-title":"Nat Med"},{"key":"R23","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1038\/nbt1183-784","article-title":"A broad host range mobilisation system for in vivo genetic engineering: transposon mutagenesis in Gram-negative bacteria","volume":"1","author":"Simon","year":"1983","journal-title":"Bio\/Technology"},{"key":"R24","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1078\/1438-4221-00292","article-title":"Exploitation of host cells by Burkholderia pseudomallei","volume":"293","author":"Stevens","year":"2004","journal-title":"Int J Med Microbiol"},{"key":"R25","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1046\/j.1365-2958.2002.03190.x","article-title":"An Inv\/Mxi-Spa-like type III protein secretion system in Burkholderia pseudomallei modulates intracellular behaviour of the pathogen","volume":"46","author":"Stevens","year":"2002","journal-title":"Mol Microbiol"},{"key":"R26","doi-asserted-by":"crossref","first-page":"4992","DOI":"10.1128\/JB.185.16.4992-4996.2003","article-title":"A Burkholderia pseudomallei type III secreted protein, BopE, facilitates bacterial invasion of epithelial cells and exhibits guanine nucleotide exchange factor activity","volume":"185","author":"Stevens","year":"2003","journal-title":"J Bacteriol"},{"key":"R27","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1128\/IAI.71.3.1405-1415.2003","article-title":"Attenuated virulence of a Burkholderia cepacia type III secretion mutant in a murine model of infection","volume":"71","author":"Tomich","year":"2003","journal-title":"Infect Immun"},{"key":"R28","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1128\/IAI.72.2.1150-1154.2004","article-title":"Type III secretion: a virulence factor delivery system essential for the pathogenicity of Burkholderia mallei","volume":"72","author":"Ulrich","year":"2004","journal-title":"Infect Immun"},{"key":"R29","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1046\/j.1365-2958.2000.01892.x","article-title":"Molecular basis of Salmonella-induced enteritis","volume":"36","author":"Wallis","year":"2000","journal-title":"Mol Microbiol"},{"key":"R30","doi-asserted-by":"crossref","first-page":"1715","DOI":"10.1016\/S0140-6736(03)13374-0","article-title":"Melioidosis","volume":"361","author":"White","year":"2003","journal-title":"Lancet"},{"key":"R31","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1099\/00222615-48-7-649","article-title":"Evidence for the presence in Burkholderia pseudomallei of a type III secretion system-associated gene cluster","volume":"48","author":"Winstanley","year":"1999","journal-title":"J Med Microbiol"},{"key":"R32","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1128\/IAI.71.1.1-12.2003","article-title":"Molecular pathogenesis of Salmonella enterica serotype Typhimurium-induced diarrhea","volume":"71","author":"Zhang","year":"2003","journal-title":"Infect Immun"},{"key":"R33","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1046\/j.1365-2958.2001.02230.x","article-title":"A Salmonella inositol polyphosphatase acts in conjunction with other bacterial effectors to promote host cell actin cytoskeleton rearrangements and bacterial internalization","volume":"39","author":"Zhou","year":"2001","journal-title":"Mol Microbiol"}],"container-title":["Microbiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.microbiologyresearch.org\/content\/journal\/micro\/10.1099\/mic.0.27146-0?crawler=true","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,11,6]],"date-time":"2020-11-06T17:30:30Z","timestamp":1604683830000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.microbiologyresearch.org\/content\/journal\/micro\/10.1099\/mic.0.27146-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,8,1]]},"references-count":33,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2004,8,1]]}},"URL":"https:\/\/doi.org\/10.1099\/mic.0.27146-0","relation":{},"ISSN":["1350-0872","1465-2080"],"issn-type":[{"value":"1350-0872","type":"print"},{"value":"1465-2080","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,8,1]]}}}