Saxifragifolin D attenuates phagosome maturation arrest in Mycobacterium tuberculosis-infected macrophages via an AMPK and VPS34-dependent pathway

详细信息    查看全文

• 作者：Jia Zhou ; Rui Xu ; Xian-zhi Du ; Xiang-dong Zhou ; Qi Li
• 关键词：Saxifragifolin D ; Phagosome maturation ; Mycobacterium tuberculosis ; VPS34
• 刊名：AMB Express
• 出版年：2017
• 出版时间：December 2017
• 年：2017
• 卷：7
• 期：1
• 全文大小：1706KB
• 刊物类别：Chemistry and Materials Science
• 刊物主题：Microbiology; Microbial Genetics and Genomics; Biotechnology;
• 出版者：Springer Berlin Heidelberg
• ISSN：2191-0855
• 卷排序：7

文摘

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.