{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T10:55:09Z","timestamp":1784804109599,"version":"3.55.0"},"reference-count":46,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2022,2,3]],"date-time":"2022-02-03T00:00:00Z","timestamp":1643846400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004396","name":"Thailand Research Fund","doi-asserted-by":"publisher","award":["NRCT5-RSA63015"],"award-info":[{"award-number":["NRCT5-RSA63015"]}],"id":[{"id":"10.13039\/501100004396","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004156","name":"Mahidol University","doi-asserted-by":"publisher","award":["Fiscal year 2018"],"award-info":[{"award-number":["Fiscal year 2018"]}],"id":[{"id":"10.13039\/501100004156","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p><jats:italic>Burkholderia pseudomallei\u2014<\/jats:italic>a causative agent of melioidosis that is endemic in Southeast Asia and Northern Australia\u2014is a Gram-negative bacterium transmitted to humans via inhalation, inoculation through skin abrasions, and ingestion. Melioidosis causes a range of clinical presentations including skin infection, pneumonia, and septicemia. Despite skin infection being one of the clinical symptoms of melioidosis, the pathogenesis of <jats:italic>B. pseudomallei<\/jats:italic> in skin fibroblasts has not yet been elucidated. In this study, we investigated <jats:italic>B. pseudomallei<\/jats:italic> pathogenesis in the HFF-1 human skin fibroblasts. On the basis of co-culture assays between different <jats:italic>B. pseudomallei<\/jats:italic> clinical strains and the HFF-1 human skin fibroblasts, we found that all <jats:italic>B. pseudomallei<\/jats:italic> strains have the ability to mediate invasion, intracellular replication, and multinucleated giant cell (MNGC) formation. Furthermore, all strains showed a significant increase in cytotoxicity in human fibroblasts, which coincides with the augmented expression of matrix metalloproteinase-2. Using <jats:italic>B. pseudomallei<\/jats:italic> mutants, we showed that the <jats:italic>B. pseudomallei<\/jats:italic> Bsa type III secretion system (T3SS) contributes to skin fibroblast pathogenesis, but O-polysaccharide, capsular polysaccharide, and short-chain dehydrogenase metabolism do not play a role in this process. Taken together, our findings reveal a probable connection for the Bsa T3SS in <jats:italic>B. pseudomallei<\/jats:italic> infection of skin fibroblasts, and this may be linked to the pathogenesis of cutaneous melioidosis.<\/jats:p>","DOI":"10.1371\/journal.pone.0261961","type":"journal-article","created":{"date-parts":[[2022,2,3]],"date-time":"2022-02-03T18:48:08Z","timestamp":1643914088000},"page":"e0261961","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":11,"title":["Burkholderia pseudomallei pathogenesis in human skin fibroblasts: A Bsa type III secretion system is involved in the invasion, multinucleated giant cell formation, and cellular damage"],"prefix":"10.1371","volume":"17","author":[{"given":"Anek","family":"Kaewpan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taksaon","family":"Duangurai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amporn","family":"Rungruengkitkun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Watcharamat","family":"Muangkaew","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tapanee","family":"Kanjanapruthipong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niramol","family":"Jitprasutwit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumate","family":"Ampawong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Passanesh","family":"Sukphopetch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Narisara","family":"Chantratita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5141-4671","authenticated-orcid":true,"given":"Pornpan","family":"Pumirat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,2,3]]},"reference":[{"key":"pone.0261961.ref001","doi-asserted-by":"crossref","first-page":"225","DOI":"10.3201\/eid0802.010164","article-title":"Public health assessment of potential biological terrorism agents","volume":"8","author":"LD Rotz","year":"2002","journal-title":"Emerging infectious diseases"},{"key":"pone.0261961.ref002","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1086\/318116","article-title":"Endemic melioidosis in tropical northern Australia: a 10-year prospective study and review of the literature","volume":"31","author":"BJ Currie","year":"2000","journal-title":"Clin Infect Dis"},{"key":"pone.0261961.ref003","doi-asserted-by":"crossref","first-page":"1498","DOI":"10.1093\/clinids\/21.6.1498","article-title":"Prognostic significance of quantitative bacteremia in septicemic melioidosis","volume":"21","author":"AL Walsh","year":"1995","journal-title":"Clin Infect Dis"},{"key":"pone.0261961.ref004","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.1586\/14787210.2014.970634","article-title":"Melioidosis: molecular aspects of pathogenesis","volume":"12","author":"JK Stone","year":"2014","journal-title":"Expert Rev Anti Infect Ther"},{"key":"pone.0261961.ref005","first-page":"1410","article-title":"Immune response to Burkholderia pseudomallei","volume":"94","author":"P. 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