title: Saxifragifolin D attenuates phagosome maturation arrest in Mycobacterium tuberculosis-infected macrophages via an AMPK and VPS34-dependent pathway.
abstract: Saxifragifolin D (SD), a traditional Chinese medicine, is a pentacyclic triterpenoid compound first isolated from Androsace umbellata. Various plant triterpenoids have been reported to exhibit antitubercular activity. In this study, THP-1-derived macrophages were infected with an attenuated M. tuberculosis (M.tb) strain, H37Ra. Intracellular replication of M.tb was evaluated by counting the colonies after 4 weeks of incubation. The results indicated that SD treatment reduced the intracellular replication of M.tb in THP-1-derived macrophages but not in A549 cells. We performed a phagosome maturation test using confocal microscopy and found that SD treatment partially attenuated the phagosome arrest induced by M.tb infection. These effects were dependent on a VPS34-associated pathway. Immunoprecipitation assays showed that SD increased intracellular UVRAG-linked VPS34, the active VPS34 complex II. However, SD had no effect on the total VPS34 pool. Moreover, the results indicated that the SD-mediated increase in VPS34 complex II activity was mediated by an AMPK-dependent pathway. Collectively, these data indicate that SD may be a promising candidate for treatment of M.tb.
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Chongqing Medical University, Yu-zhong District, Chongqing, 400016, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Respiratory Medicine, The Second Affiliated Hospital, Chongqing Medical University, No.74 Linjiang Road, Yu-zhong District, Chongqing, 400010, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Xu
authors.affiliation: Department of Respiratory Medicine, The Second Affiliated Hospital, Chongqing Medical University, No.74 Linjiang Road, Yu-zhong District, Chongqing, 400010, China. dxzdjy868@sina.com.
authors.forename: Xian-Zhi
authors.initials: XZ
authors.lastname: Du
authors.affiliation: Department of Respiratory Medicine, the First Affiliated Hospital of Hainan Medical University, Haikou, Hainan province, 570102, China.
authors.forename: Xiang-Dong
authors.initials: XD
authors.lastname: Zhou
authors.affiliation: Department of Respiratory Medicine, the First Affiliated Hospital of Hainan Medical University, Haikou, Hainan province, 570102, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Li
keywords: Mycobacterium tuberculosis; Phagosome maturation; Saxifragifolin D; VPS34