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Lipids are an important nutrient for the intracellular survival of <jats:italic>M<\/jats:italic>. <jats:italic>leprae<\/jats:italic>. In this study, we attempted to determine the intracellular lipid composition and underlying mechanisms for changes in host cell lipid metabolism induced by <jats:italic>M<\/jats:italic>. <jats:italic>leprae<\/jats:italic> infection. Using high-performance thin-layer chromatography (HPTLC), we demonstrated specific induction of triacylglycerol (TAG) production in human macrophage THP-1 cells following <jats:italic>M<\/jats:italic>. <jats:italic>leprae<\/jats:italic> infection. We then used [<jats:sup>14<\/jats:sup>C] stearic acid tracing to show incorporation of this newly synthesized host cell TAG into <jats:italic>M<\/jats:italic>. <jats:italic>leprae<\/jats:italic>. In parallel with TAG accumulation, expression of host glycerol-3-phosphate acyltransferase 3 (GPAT3), a key enzyme in <jats:italic>de novo<\/jats:italic> TAG synthesis, was significantly increased in <jats:italic>M<\/jats:italic>. <jats:italic>leprae<\/jats:italic>-infected cells. CRISPR\/Cas9 genome editing of GPAT3 in THP-1 cells (<jats:italic>GPAT3<\/jats:italic> KO) dramatically reduced accumulation of TAG following <jats:italic>M<\/jats:italic>. <jats:italic>leprae<\/jats:italic> infection, intracellular mycobacterial load, and bacteria viability. These results together suggest that <jats:italic>M<\/jats:italic>. <jats:italic>leprae<\/jats:italic> induces host GPAT3 expression to facilitate TAG accumulation within macrophages to maintain a suitable environment that is crucial for intracellular survival of these bacilli.<\/jats:p>","DOI":"10.1371\/journal.pone.0249184","type":"journal-article","created":{"date-parts":[[2021,3,26]],"date-time":"2021-03-26T17:36:54Z","timestamp":1616780214000},"page":"e0249184","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":9,"title":["Mycobacterium leprae promotes triacylglycerol de novo synthesis through induction of GPAT3 expression in human premonocytic THP-1 cells"],"prefix":"10.1371","volume":"16","author":[{"given":"Kazunari","family":"Tanigawa","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuhiro","family":"Hayashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kotaro","family":"Hama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2544-2134","authenticated-orcid":true,"given":"Atsushi","family":"Yamashita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2407-5368","authenticated-orcid":true,"given":"Kazuaki","family":"Yokoyama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuqian","family":"Luo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akira","family":"Kawashima","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yumi","family":"Maeda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2167-9182","authenticated-orcid":true,"given":"Yasuhiro","family":"Nakamura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayako","family":"Harada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8896-0764","authenticated-orcid":true,"given":"Mitsuo","family":"Kiriya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ken","family":"Karasawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8659-4660","authenticated-orcid":true,"given":"Koichi","family":"Suzuki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2021,3,26]]},"reference":[{"key":"pone.0249184.ref001","first-page":"389","volume":"94","author":"WHO","year":"2019","journal-title":"Weekly epidemiological record"},{"issue":"3","key":"pone.0249184.ref002","first-page":"255","article-title":"Classification of leprosy according to immunity. 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