A Case of Relapsed Leprosy Successfully Treated With Sparfloxacin

Suga, Chizuka

doi:10.1001/archderm.1996.03890350141036

Cited by 4 publications

(1 citation statement)

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“…However, for GPAT3 KO cells the M. leprae pseudogene expression was rapidly reduced compared to that seen for wild-type cells (Fig 4E). The expression of M. leprae hsp70 mRNA was used as a control, since its expression level is stable [26] and did not change in both cells. These results suggest that the viability of M. leprae was lower in GPAT3 KO cells.…”

Section: Gpat3 Is Essential For the Intracellular Survival Of M Lepraementioning

confidence: 99%

Mycobacterium leprae promotes triacylglycerol de novo synthesis through induction of GPAT3 expression in human premonocytic THP-1 cells

et al. 2021

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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.

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Section: Gpat3 Is Essential For the Intracellular Survival Of M Lepraementioning

confidence: 99%