{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T18:16:48Z","timestamp":1776363408293,"version":"3.51.2"},"reference-count":58,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2019,11,26]],"date-time":"2019-11-26T00:00:00Z","timestamp":1574726400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000774","name":"Defense Threat Reduction Agency","doi-asserted-by":"publisher","award":["CBCall14-AMD2-CBM-05-2-0015"],"award-info":[{"award-number":["CBCall14-AMD2-CBM-05-2-0015"]}],"id":[{"id":"10.13039\/100000774","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Melioidosis is an emerging disease that is caused by the facultative intracellular pathogen Burkholderia pseudomallei. It is intrinsically resistant to many antibiotics and host risk factors play a major role in susceptibility to infection. Currently, there is no human or animal vaccine against melioidosis. In this study, multiple B. pseudomallei MSHR668 deletion mutants were evaluated as live attenuated vaccines in the sensitive BALB\/c mouse model of melioidosis. The most efficacious vaccines after an intraperitoneal challenge with 50-fold over the 50% median lethal dose (MLD50) with B. pseudomallei K96243 were 668 \u0394hisF and 668 \u0394ilvI. Both vaccines completely protected mice in the acute phase of infection and showed significant protection (50% survivors) during the chronic phase of infection. The spleens of the survivors that were examined were sterile. Splenocytes from mice vaccinated with 668 \u0394hisF and 668 \u0394ilvI expressed higher amounts of IFN-\u03b3 after stimulation with B. pseudomallei antigens than splenocytes from mice vaccinated with less protective candidates. Finally, we demonstrate that 668 \u0394hisF is nonlethal in immunocompromised NOD\/SCID mice. Our results show that 668 \u0394hisF and 668 \u0394ilvI provide protective cell-mediated immune responses in the acute phase of infection and promote long term survival in the sensitive BALB\/c mouse model of melioidosis.<\/jats:p>","DOI":"10.3390\/vaccines7040196","type":"journal-article","created":{"date-parts":[[2019,11,26]],"date-time":"2019-11-26T10:57:27Z","timestamp":1574765847000},"page":"196","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Deletion of Two Genes in Burkholderia pseudomallei MSHR668 That Target Essential Amino Acids Protect Acutely Infected BALB\/c Mice and Promote Long Term Survival"],"prefix":"10.3390","volume":"7","author":[{"given":"Kei","family":"Amemiya","sequence":"first","affiliation":[{"name":"Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer L.","family":"Dankmeyer","sequence":"additional","affiliation":[{"name":"Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergei S.","family":"Biryukov","sequence":"additional","affiliation":[{"name":"Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sylvia R.","family":"Trevi\u00f1o","sequence":"additional","affiliation":[{"name":"Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher P.","family":"Klimko","sequence":"additional","affiliation":[{"name":"Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sherry M.","family":"Mou","sequence":"additional","affiliation":[{"name":"Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David P.","family":"Fetterer","sequence":"additional","affiliation":[{"name":"Biostatistical Services, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Preston G.","family":"Garnes","sequence":"additional","affiliation":[{"name":"Biostatistical Services, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher K.","family":"Cote","sequence":"additional","affiliation":[{"name":"Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patricia L.","family":"Worsham","sequence":"additional","affiliation":[{"name":"Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"DeShazer","sequence":"additional","affiliation":[{"name":"Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,11,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"15008","DOI":"10.1038\/nmicrobiol.2015.8","article-title":"Predicted global distribution of Burkholderia pseudomallei and burden of melioidosis","volume":"1","author":"Limmathurotsakul","year":"2016","journal-title":"Nat. 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