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The antibiotic resistance profile and ability to infect via aerosol of these organisms and the absence of protective vaccines have led to their classification as major biothreats and select agents. Although documented infections by these bacteria date back over 100 years, relatively little is known about their virulence and pathogenicity mechanisms. We used in silico genomic subtraction to generate their virulome, a set of 650 putative virulence-related genes shared by\n            <jats:italic>B. pseudomallei<\/jats:italic>\n            and\n            <jats:italic>B. mallei<\/jats:italic>\n            but not present in five closely related nonpathogenic\n            <jats:italic>Burkholderia<\/jats:italic>\n            species. Although most of these genes are clustered in putative operons, the number of targets for mutant construction and verification of reduced virulence in animal models is formidable. Therefore,\n            <jats:italic>Galleria mellonella<\/jats:italic>\n            (wax moth) larvae were evaluated as a surrogate host; we found that\n            <jats:italic>B. pseudomallei<\/jats:italic>\n            and\n            <jats:italic>B. mallei<\/jats:italic>\n            , but not other phylogenetically related bacteria, were highly pathogenic for this insect. More importantly, four previously characterized\n            <jats:italic>B. mallei<\/jats:italic>\n            mutants with reduced virulence in hamsters or mice had similarly reduced virulence in\n            <jats:italic>G. mellonella<\/jats:italic>\n            larvae. Site-specific inactivation of selected genes in the computationally derived virulome identified three new potential virulence genes, each of which was required for rapid and efficient killing of larvae. Thus, this approach may provide a means to quickly identify high-probability virulence genes in\n            <jats:italic>B. pseudomallei, B. mallei<\/jats:italic>\n            , and other pathogens.\n          <\/jats:p>","DOI":"10.1128\/jb.01735-07","type":"journal-article","created":{"date-parts":[[2008,1,26]],"date-time":"2008-01-26T01:54:16Z","timestamp":1201312456000},"page":"2306-2313","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":57,"title":["Comparative Genomics and an Insect Model Rapidly Identify Novel Virulence Genes of\n            <i>Burkholderia mallei<\/i>"],"prefix":"10.1128","volume":"190","author":[{"given":"Mark A.","family":"Schell","sequence":"first","affiliation":[{"name":"Department of Microbiology, University of Georgia, Athens, Georgia 30602"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lyla","family":"Lipscomb","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Georgia, Athens, Georgia 30602"}],"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 21702-5011"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.28.10.2331-2334.1990"},{"key":"e_1_3_2_3_2","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1111\/j.1365-2672.1997.tb02867.x","volume":"82","year":"1997","unstructured":"Brook, M. 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