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Mycobacterium leprae promotes triacylglycerol de novo synthesis through induction of GPAT3 expression in human premonocytic THP-1 cells.
| العنوان: | Mycobacterium leprae promotes triacylglycerol de novo synthesis through induction of GPAT3 expression in human premonocytic THP-1 cells. |
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| المؤلفون: | Kazunari Tanigawa, Yasuhiro Hayashi, Kotaro Hama, Atsushi Yamashita, Kazuaki Yokoyama, Yuqian Luo, Akira Kawashima, Yumi Maeda, Yasuhiro Nakamura, Ayako Harada, Mitsuo Kiriya, Ken Karasawa, Koichi Suzuki |
| المصدر: | PLoS ONE, Vol 16, Iss 3, p e0249184 (2021) |
| بيانات النشر: | Public Library of Science (PLoS), 2021. |
| سنة النشر: | 2021 |
| المجموعة: | LCC:Medicine LCC:Science |
| مصطلحات موضوعية: | Medicine, Science |
| الوصف: | Mycobacterium leprae (M. leprae) is the etiological agent of leprosy, and the skin lesions of lepromatous leprosy are filled with numerous foamy or xanthomatous histiocytes that are parasitized by M. leprae. Lipids are an important nutrient for the intracellular survival of M. leprae. In this study, we attempted to determine the intracellular lipid composition and underlying mechanisms for changes in host cell lipid metabolism induced by M. leprae infection. Using high-performance thin-layer chromatography (HPTLC), we demonstrated specific induction of triacylglycerol (TAG) production in human macrophage THP-1 cells following M. leprae infection. We then used [14C] stearic acid tracing to show incorporation of this newly synthesized host cell TAG into M. leprae. In parallel with TAG accumulation, expression of host glycerol-3-phosphate acyltransferase 3 (GPAT3), a key enzyme in de novo TAG synthesis, was significantly increased in M. leprae-infected cells. CRISPR/Cas9 genome editing of GPAT3 in THP-1 cells (GPAT3 KO) dramatically reduced accumulation of TAG following M. leprae infection, intracellular mycobacterial load, and bacteria viability. These results together suggest that M. leprae induces host GPAT3 expression to facilitate TAG accumulation within macrophages to maintain a suitable environment that is crucial for intracellular survival of these bacilli. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1932-6203 |
| Relation: | https://doaj.org/toc/1932-6203 |
| DOI: | 10.1371/journal.pone.0249184 |
| URL الوصول: | https://doaj.org/article/9c48a7df449845b6b5b8d1049aeecf86 |
| رقم الانضمام: | edsdoj.9c48a7df449845b6b5b8d1049aeecf86 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 19326203 |
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| DOI: | 10.1371/journal.pone.0249184 |