{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T17:56:00Z","timestamp":1791741360317,"version":"4.3.4"},"reference-count":50,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2015,2,4]],"date-time":"2015-02-04T00:00:00Z","timestamp":1423008000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2015,2,4]],"date-time":"2015-02-04T00:00:00Z","timestamp":1423008000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The Type VI Secretion System cluster 1 (T6SS1) is essential for the pathogenesis of\n                    <jats:italic>Burkholderia pseudomallei<\/jats:italic>\n                    , the causative agent of melioidosis, a disease endemic in the tropics. Inside host cells,\n                    <jats:italic>B. pseudomallei<\/jats:italic>\n                    escapes into the cytosol and through T6SS1, induces multinucleated giant cell (MNGC) formation that is thought to be important for bacterial cell to cell spread. The hemolysin-coregulated protein (Hcp) is both a T6SS substrate, as well as postulated to form part of the T6SS secretion tube. Our structural study reveals that Hcp1 forms hexameric rings similar to the other Hcp homologs but has an extended loop (Asp40-Arg56) that deviates significantly in position compared to other Hcp structures and may act as a key contact point between adjacent hexameric rings. When two residues within the loop were mutated, the mutant proteins were unable to stack as dodecamers, suggesting defective tube assembly. Moreover, infection with a bacterial mutant containing\n                    <jats:italic>in situ<\/jats:italic>\n                    substitution of these\n                    <jats:italic>hcp1<\/jats:italic>\n                    residues abolishes Hcp1 secretion inside infected cells and MNGC formation. We further show that Hcp has the ability to preferentially bind to the surface of antigen-presenting cells, which may contribute to its immunogenicity in inducing high titers of antibodies seen in melioidosis patients.\n                  <\/jats:p>","DOI":"10.1038\/srep08235","type":"journal-article","created":{"date-parts":[[2015,2,4]],"date-time":"2015-02-04T05:21:05Z","timestamp":1423027265000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["Extended Loop Region of Hcp1 is Critical for the Assembly and Function of Type VI Secretion System in Burkholderia pseudomallei"],"prefix":"10.1038","volume":"5","author":[{"given":"Yan Ting","family":"Lim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chacko","family":"Jobichen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jocelyn","family":"Wong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Direk","family":"Limmathurotsakul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaowei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yahua","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manfred","family":"Raida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nalini","family":"Srinivasan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul Anthony","family":"MacAry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Sivaraman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunn-Hwen","family":"Gan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,2,4]]},"reference":[{"key":"BFsrep08235_CR1","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1128\/CMR.4.1.52","volume":"4","author":"DA Dance","year":"1991","unstructured":"Dance, D. A. Melioidosis: the tip of the iceberg? Clin Microbiol Rev 4, 52\u201360 (1991).","journal-title":"Clin Microbiol Rev"},{"key":"BFsrep08235_CR2","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1128\/CMR.18.2.383-416.2005","volume":"18","author":"AC Cheng","year":"2005","unstructured":"Cheng, A. C. & Currie, B. J. Melioidosis: epidemiology, pathophysiology and management. Clin Microbiol Rev 18, 383\u2013416 (2005).","journal-title":"Clin Microbiol Rev"},{"key":"BFsrep08235_CR3","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/S0001-706X(99)00059-5","volume":"74","author":"DA Dance","year":"2000","unstructured":"Dance, D. A. Melioidosis as an emerging global problem. Acta Trop 74, 115\u20139 (2000).","journal-title":"Acta Trop"},{"key":"BFsrep08235_CR4","doi-asserted-by":"publisher","first-page":"456","DOI":"10.1128\/IAI.00503-08","volume":"77","author":"S Chanchamroen","year":"2009","unstructured":"Chanchamroen, S., Kewcharoenwong, C., Susaengrat, W., Ato, M. & Lertmemongkolchai, G. Human polymorphonuclear neutrophil responses to Burkholderia pseudomallei in healthy and diabetic subjects. Infect Immun 77, 456\u201363 (2009).","journal-title":"Infect Immun"},{"key":"BFsrep08235_CR5","first-page":"5377","volume":"68","author":"W Kespichayawattana","year":"2000","unstructured":"Kespichayawattana, W., Rattanachetkul, S., Wanun, T., Utaisincharoen, P. & Sirisinha, S. Burkholderia pseudomallei induces cell fusion and actin-associated membrane protrusion: a possible mechanism for cell-to-cell spreading. Infect Immun 68, 5377\u201384 (2000).","journal-title":"Burkholderia pseudomallei"},{"key":"BFsrep08235_CR6","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1111\/j.1365-2958.2004.04528.x","volume":"56","author":"MP Stevens","year":"2005","unstructured":"Stevens, M. P. et al. Identification of a bacterial factor required for actin-based motility of Burkholderia pseudomallei. Mol Microbiol 56, 40\u201353 (2005).","journal-title":"Mol Microbiol"},{"key":"BFsrep08235_CR7","doi-asserted-by":"publisher","first-page":"12095","DOI":"10.1073\/pnas.1107183108","volume":"108","author":"CT French","year":"2011","unstructured":"French, C. T. et al. Dissection of the Burkholderia intracellular life cycle using a photothermal nanoblade. Proc Natl Acad Sci U S A 108, 12095\u2013100 (2011).","journal-title":"Proc Natl Acad Sci U S A"},{"key":"BFsrep08235_CR8","doi-asserted-by":"publisher","first-page":"6556","DOI":"10.1128\/JB.187.18.6556-6560.2005","volume":"187","author":"S Suparak","year":"2005","unstructured":"Suparak, S. et al. Multinucleated giant cell formation and apoptosis in infected host cells is mediated by Burkholderia pseudomallei type III secretion protein BipB. J Bacteriol 187, 6556\u201360 (2005).","journal-title":"J Bacteriol"},{"key":"BFsrep08235_CR9","first-page":"184","volume":"40","author":"P Utaisincharoen","year":"2006","unstructured":"Utaisincharoen, P., Arjcharoen, S., Limposuwan, K., Tungpradabkul, S. & Sirisinha, S. Burkholderia pseudomallei RpoS regulates multinucleated giant cell formation and inducible nitric oxide synthase expression in mouse macrophage cell line (RAW 264.7). Microb Pathog 40, 184\u20139 (2006).","journal-title":"Burkholderia pseudomallei"},{"key":"BFsrep08235_CR10","first-page":"88","volume":"78","author":"MN Burtnick","year":"2010","unstructured":"Burtnick, M. N., DeShazer, D., Nair, V., Gherardini, F. C. & Brett, P. J. Burkholderia mallei cluster 1 type VI secretion mutants exhibit growth and actin polymerization defects in RAW 264.7 murine macrophages. Infect Immun 78, 88\u201399 (2010).","journal-title":"Burkholderia mallei"},{"key":"BFsrep08235_CR11","doi-asserted-by":"publisher","first-page":"1512","DOI":"10.1128\/IAI.01218-10","volume":"79","author":"MN Burtnick","year":"2011","unstructured":"Burtnick, M. N. et al. The cluster 1 type VI secretion system is a major virulence determinant in Burkholderia pseudomallei. Infect Immun 79, 1512\u201325 (2011).","journal-title":"Infect Immun"},{"key":"BFsrep08235_CR12","doi-asserted-by":"publisher","first-page":"3064","DOI":"10.1128\/IAI.05148-11","volume":"79","author":"Y Chen","year":"2011","unstructured":"Chen, Y. et al. Regulation of type VI secretion system during Burkholderia pseudomallei infection. Infect Immun 79, 3064\u201373 (2011).","journal-title":"Infect Immun"},{"key":"BFsrep08235_CR13","first-page":"e1001068","volume":"6","author":"S Schwarz","year":"2010","unstructured":"Schwarz, S. et al. Burkholderia type VI secretion systems have distinct roles in eukaryotic and bacterial cell interactions. PLoS Pathog 6, e1001068 (2010).","journal-title":"Burkholderia"},{"key":"BFsrep08235_CR14","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.chom.2009.12.007","volume":"7","author":"RD Hood","year":"2010","unstructured":"Hood, R. D. et al. A type VI secretion system of Pseudomonas aeruginosa targets a toxin to bacteria. Cell Host Microbe 7, 25\u201337 (2010).","journal-title":"Cell Host Microbe"},{"key":"BFsrep08235_CR15","doi-asserted-by":"publisher","first-page":"3576","DOI":"10.1128\/IAI.01262-05","volume":"74","author":"S Pilatz","year":"2006","unstructured":"Pilatz, S. et al. Identification of Burkholderia pseudomallei genes required for the intracellular life cycle and in vivo virulence. Infect Immun 74, 3576\u201386 (2006).","journal-title":"Infect Immun"},{"key":"BFsrep08235_CR16","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1111\/j.1365-2958.2010.07124.x","volume":"76","author":"GW Sun","year":"2010","unstructured":"Sun, G. W. et al. Identification of a regulatory cascade controlling Type III Secretion System 3 gene expression in Burkholderia pseudomallei. Mol Microbiol 76, 677\u201389 (2010).","journal-title":"Mol Microbiol"},{"key":"BFsrep08235_CR17","doi-asserted-by":"publisher","first-page":"1102","DOI":"10.1098\/rstb.2011.0209","volume":"367","author":"E Cascales","year":"2012","unstructured":"Cascales, E. & Cambillau, C. Structural biology of type VI secretion systems. Philos Trans R Soc Lond B Biol Sci 367, 1102\u201311 (2012).","journal-title":"Philos Trans R Soc Lond B Biol Sci"},{"key":"BFsrep08235_CR18","doi-asserted-by":"publisher","first-page":"4154","DOI":"10.1073\/pnas.0813360106","volume":"106","author":"PG Leiman","year":"2009","unstructured":"Leiman, P. G. et al. Type VI secretion apparatus and phage tail-associated protein complexes share a common evolutionary origin. Proc Natl Acad Sci U S A 106, 4154\u20139 (2009).","journal-title":"Proc Natl Acad Sci U S A"},{"key":"BFsrep08235_CR19","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1146\/annurev-micro-121809-151619","volume":"66","author":"JM Silverman","year":"2012","unstructured":"Silverman, J. M., Brunet, Y. R., Cascales, E. & Mougous, J. D. Structure and regulation of the type VI secretion system. Annu Rev Microbiol 66, 453\u201372 (2012).","journal-title":"Annu Rev Microbiol"},{"key":"BFsrep08235_CR20","doi-asserted-by":"publisher","first-page":"584","DOI":"10.1016\/j.molcel.2013.07.025","volume":"51","author":"JM Silverman","year":"2013","unstructured":"Silverman, J. M. et al. Haemolysin coregulated protein is an exported receptor and chaperone of type VI secretion substrates. Mol Cell 51, 584\u201393 (2013).","journal-title":"Mol Cell"},{"key":"BFsrep08235_CR21","doi-asserted-by":"publisher","first-page":"1526","DOI":"10.1126\/science.1128393","volume":"312","author":"JD Mougous","year":"2006","unstructured":"Mougous, J. D. et al. A virulence locus of Pseudomonas aeruginosa encodes a protein secretion apparatus. Science 312, 1526\u201330 (2006).","journal-title":"Science"},{"key":"BFsrep08235_CR22","doi-asserted-by":"publisher","first-page":"e12910","DOI":"10.1371\/journal.pone.0012910","volume":"5","author":"C Jobichen","year":"2010","unstructured":"Jobichen, C. et al. Structural basis for the secretion of EvpC: a key type VI secretion system protein from Edwardsiella tarda. PLoS One 5, e12910 (2010).","journal-title":"PLoS One"},{"key":"BFsrep08235_CR23","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1007\/s10969-011-9107-1","volume":"12","author":"J Osipiuk","year":"2011","unstructured":"Osipiuk, J. et al. Crystal structure of secretory protein Hcp3 from Pseudomonas aeruginosa. J Struct Funct Genomics 12, 21\u20136 (2011).","journal-title":"J Struct Funct Genomics"},{"key":"BFsrep08235_CR24","doi-asserted-by":"publisher","first-page":"e86918","DOI":"10.1371\/journal.pone.0086918","volume":"9","author":"B Douzi","year":"2014","unstructured":"Douzi, B. et al. Crystal structure and self-interaction of the type VI secretion tail-tube protein from enteroaggregative Escherichia coli. PLoS One 9, e86918 (2014).","journal-title":"PLoS One"},{"key":"BFsrep08235_CR25","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1002\/embr.201337936","volume":"15","author":"YR Brunet","year":"2014","unstructured":"Brunet, Y. R., Henin, J., Celia, H. & Cascales, E. Type VI secretion and bacteriophage tail tubes share a common assembly pathway. EMBO Rep 15, 315\u201321 (2014).","journal-title":"EMBO Rep"},{"key":"BFsrep08235_CR26","doi-asserted-by":"publisher","first-page":"3733","DOI":"10.1073\/pnas.0712247105","volume":"105","author":"ER Ballister","year":"2008","unstructured":"Ballister, E. R., Lai, A. H., Zuckermann, R. N., Cheng, Y. & Mougous, J. D. In vitro self-assembly of tailorable nanotubes from a simple protein building block. Proc Natl Acad Sci U S A 105, 3733\u20138 (2008).","journal-title":"Proc Natl Acad Sci U S A"},{"key":"BFsrep08235_CR27","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1093\/nar\/26.1.316","volume":"26","author":"L Holm","year":"1998","unstructured":"Holm, L. & Sander, C. Touring protein fold space with Dali\/FSSP. Nucleic Acids Res 26, 316\u20139 (1998).","journal-title":"Nucleic Acids Res"},{"key":"BFsrep08235_CR28","doi-asserted-by":"publisher","first-page":"1447","DOI":"10.1111\/j.1462-5822.2005.00569.x","volume":"7","author":"GW Sun","year":"2005","unstructured":"Sun, G. W., Lu, J., Pervaiz, S., Cao, W. P. & Gan, Y. H. Caspase-1 dependent macrophage death induced by Burkholderia pseudomallei. Cell Microbiol 7, 1447\u201358 (2005).","journal-title":"Cell Microbiol"},{"key":"BFsrep08235_CR29","doi-asserted-by":"publisher","first-page":"3678","DOI":"10.1099\/mic.0.041277-0","volume":"156","author":"G Suarez","year":"2010","unstructured":"Suarez, G., Sierra, J. C., Kirtley, M. L. & Chopra, A. K. Role of Hcp, a type 6 secretion system effector, of Aeromonas hydrophila in modulating activation of host immune cells. Microbiology 156, 3678\u201388 (2010).","journal-title":"Microbiology"},{"key":"BFsrep08235_CR30","doi-asserted-by":"publisher","first-page":"15508","DOI":"10.1073\/pnas.0706532104","volume":"104","author":"S Pukatzki","year":"2007","unstructured":"Pukatzki, S., Ma, A. T., Revel, A. T., Sturtevant, D. & Mekalanos, J. J. Type VI secretion system translocates a phage tail spike-like protein into target cells where it cross-links actin. Proc Natl Acad Sci U S A 104, 15508\u201313 (2007).","journal-title":"Proc Natl Acad Sci U S A"},{"key":"BFsrep08235_CR31","doi-asserted-by":"publisher","first-page":"1664","DOI":"10.1016\/j.bbamcr.2014.03.018","volume":"1843","author":"A Zoued","year":"2014","unstructured":"Zoued, A. et al. Architecture and assembly of the Type VI secretion system. Biochim Biophys Acta 1843, 1664\u20131673 (2014).","journal-title":"Biochim Biophys Acta"},{"key":"BFsrep08235_CR32","doi-asserted-by":"publisher","first-page":"2841","DOI":"10.1128\/JB.01775-07","volume":"190","author":"HY Wu","year":"2008","unstructured":"Wu, H. Y., Chung, P. C., Shih, H. W., Wen, S. R. & Lai, E. M. Secretome analysis uncovers an Hcp-family protein secreted via a type VI secretion system in Agrobacterium tumefaciens. J Bacteriol 190, 2841\u201350 (2008).","journal-title":"J Bacteriol"},{"key":"BFsrep08235_CR33","doi-asserted-by":"publisher","first-page":"2941","DOI":"10.1128\/IAI.01266-10","volume":"79","author":"ST Miyata","year":"2011","unstructured":"Miyata, S. T., Kitaoka, M., Brooks, T. M., McAuley, S. B. & Pukatzki, S. Vibrio cholerae requires the type VI secretion system virulence factor VasX to kill Dictyostelium discoideum. Infect Immun 79, 2941\u20139 (2011).","journal-title":"Infect Immun"},{"key":"BFsrep08235_CR34","doi-asserted-by":"publisher","first-page":"1466","DOI":"10.1111\/j.1365-2958.2007.05734.x","volume":"64","author":"MA Schell","year":"2007","unstructured":"Schell, M. A. et al. Type VI secretion is a major virulence determinant in Burkholderia mallei. Mol Microbiol 64, 1466\u201385 (2007).","journal-title":"Mol Microbiol"},{"key":"BFsrep08235_CR35","doi-asserted-by":"publisher","first-page":"1445","DOI":"10.1128\/IAI.01368-13","volume":"82","author":"S Schwarz","year":"2014","unstructured":"Schwarz, S. et al. VgrG-5 is a Burkholderia type VI secretion system-exported protein required for multinucleated giant cell formation and virulence. Infect Immun 82, 1445\u201352 (2014).","journal-title":"Infect Immun"},{"key":"BFsrep08235_CR36","doi-asserted-by":"publisher","first-page":"1436","DOI":"10.1128\/IAI.01367-13","volume":"82","author":"IJ Toesca","year":"2014","unstructured":"Toesca, I. J., French, C. T. & Miller, J. F. The Type VI secretion system spike protein VgrG5 mediates membrane fusion during intercellular spread by pseudomallei group Burkholderia species. Infect Immun 82, 1436\u201344 (2014).","journal-title":"Infect Immun"},{"key":"BFsrep08235_CR37","doi-asserted-by":"publisher","first-page":"1528","DOI":"10.1073\/pnas.0510322103","volume":"103","author":"S Pukatzki","year":"2006","unstructured":"Pukatzki, S. et al. Identification of a conserved bacterial protein secretion system in Vibrio cholerae using the Dictyostelium host model system. Proc Natl Acad Sci U S A 103, 1528\u201333 (2006).","journal-title":"Proc Natl Acad Sci U S A"},{"key":"BFsrep08235_CR38","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/0378-1119(89)90358-2","volume":"77","author":"SN Ho","year":"1989","unstructured":"Ho, S. N., Hunt, H. D., Horton, R. M., Pullen, J. K. & Pease, L. R. Site-directed mutagenesis by overlap extension using the polymerase chain reaction. Gene 77, 51\u20139 (1989).","journal-title":"Gene"},{"key":"BFsrep08235_CR39","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1107\/S0907444997005398","volume":"53","author":"TC Terwilliger","year":"1997","unstructured":"Terwilliger, T. C. & Berendzen, J. Bayesian correlated MAD phasing. Acta Crystallogr D Biol Crystallogr 53, 571\u20139 (1997).","journal-title":"Acta Crystallogr D Biol Crystallogr"},{"key":"BFsrep08235_CR40","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1016\/S0076-6879(97)76066-X","volume":"Vol. 276","author":"Z Otwinowski","year":"1997","unstructured":"Otwinowski, Z. & Minor, W. Processing of X-ray diffraction data collected in oscillation mode. in Methods in enzymology, Vol. 276, 307\u2013326 (Academic press 1997).","journal-title":"Methods in enzymology,"},{"key":"BFsrep08235_CR41","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1107\/S0907444909052925","volume":"66","author":"PD Adams","year":"2010","unstructured":"Adams, P. D. et al. PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr D Biol Crystallogr 66, 213\u201321 (2010).","journal-title":"Acta Crystallogr D Biol Crystallogr"},{"key":"BFsrep08235_CR42","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1107\/S0907444902018048","volume":"59","author":"TC Terwilliger","year":"2003","unstructured":"Terwilliger, T. C. Automated side-chain model building and sequence assignment by template matching. Acta Crystallogr D Biol Crystallogr 59, 45\u20139 (2003).","journal-title":"Acta Crystallogr D Biol Crystallogr"},{"key":"BFsrep08235_CR43","doi-asserted-by":"publisher","first-page":"2126","DOI":"10.1107\/S0907444904019158","volume":"60","author":"P Emsley","year":"2004","unstructured":"Emsley, P. & Cowtan, K. Coot: model-building tools for molecular graphics. Acta Crystallogr D Biol Crystallogr 60, 2126\u201332 (2004).","journal-title":"Acta Crystallogr D Biol Crystallogr"},{"key":"BFsrep08235_CR44","doi-asserted-by":"publisher","first-page":"4651","DOI":"10.1529\/biophysj.106.081372","volume":"90","author":"PH Brown","year":"2006","unstructured":"Brown, P. H. & Schuck, P. Macromolecular size-and-shape distributions by sedimentation velocity analytical ultracentrifugation. Biophys J 90, 4651\u201361 (2006).","journal-title":"Biophys J"},{"key":"BFsrep08235_CR45","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1007\/s00430-003-0191-0","volume":"193","author":"K Mori","year":"2004","unstructured":"Mori, K. et al. The functional interaction between CD98 and CD147 in regulation of virus-induced cell fusion and osteoclast formation. Med Microbiol Immunol 193, 155\u201362 (2004).","journal-title":"Med Microbiol Immunol"},{"key":"BFsrep08235_CR46","doi-asserted-by":"publisher","first-page":"4992","DOI":"10.1128\/JB.185.16.4992-4996.2003","volume":"185","author":"MP Stevens","year":"2003","unstructured":"Stevens, M. P. et al. A Burkholderia pseudomallei type III secreted protein, BopE, facilitates bacterial invasion of epithelial cells and exhibits guanine nucleotide exchange factor activity. J Bacteriol 185, 4992\u20136 (2003).","journal-title":"J Bacteriol"},{"key":"BFsrep08235_CR47","doi-asserted-by":"publisher","first-page":"846","DOI":"10.1093\/clinids\/19.5.846","volume":"19","author":"Y Suputtamongkol","year":"1994","unstructured":"Suputtamongkol, Y. et al. Ceftazidime vs. amoxicillin\/clavulanate in the treatment of severe melioidosis. Clin Infect Dis 19, 846\u201353 (1994).","journal-title":"Clin Infect Dis"},{"key":"BFsrep08235_CR48","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/0378-1119(94)90324-7","volume":"145","author":"A Schafer","year":"1994","unstructured":"Schafer, A. et al. Small mobilizable multi-purpose cloning vectors derived from the Escherichia coli plasmids pK18 and pK19: selection of defined deletions in the chromosome of Corynebacterium glutamicum. Gene 145, 69\u201373 (1994).","journal-title":"Gene"},{"key":"BFsrep08235_CR49","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1128\/IAI.70.2.504-511.2002","volume":"70","author":"B Liu","year":"2002","unstructured":"Liu, B., Koo, G. C., Yap, E. H., Chua, K. L. & Gan, Y. H. Model of differential susceptibility to mucosal Burkholderia pseudomallei infection. Infect Immun 70, 504\u201311 (2002).","journal-title":"Infect Immun"},{"key":"BFsrep08235_CR50","doi-asserted-by":"publisher","first-page":"784","DOI":"10.1038\/nbt1183-784","volume":"1","author":"R Simon","year":"1983","unstructured":"Simon, R., Priefer, U. & Puhler, A. A Broad Host Range Mobilization System for In Vivo Genetic Engineering: Transposon Mutagenesis in Gram Negative Bacteria. Nat Biotech 1, 784\u2013791 (1983).","journal-title":"Nat Biotech"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep08235","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep08235.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep08235.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T19:38:38Z","timestamp":1672947518000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep08235"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,2,4]]},"references-count":50,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2015,7,15]]}},"alternative-id":["BFsrep08235"],"URL":"https:\/\/doi.org\/10.1038\/srep08235","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,2,4]]},"assertion":[{"value":"6 August 2014","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 January 2015","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 February 2015","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"8235"}}