title: Autophagy regulation revealed by SapM-induced block of autophagosome-lysosome fusion via binding RAB7.
abstract: The mechanism underlying autophagy alteration by mycobacterium tuberculosis remains unclear. Our previous study shows LpqH, a lipoprotein of mycobacterium tuberculosis, can cause autophagosomes accumulation in murine macrophages. It is well known that SapM, another virulence factor, plays an important role in blocking phagosome-endosome fusion. However, the mechanism that SapM interferes with autophagy remains poorly defined. In this study, we report that SapM suppresses the autophagy flux by blocking autophagosome fusion with lysosome. Exposure to SapM results in accumulations of autophagosomes and decreased co-localization of autophagosome with lysosome. Molecularly, Rab7, a small GTPase, is blocked by SapM through its CT domain and is prevented from involvement of autophagosome-lysosome fusion. In conclusion, our study reveals that SapM takes Rab7 as a previously unknown target to govern a distinct molecular mechanism underlying autophagosome-lysosome fusion, which may bring light to a new thought about developing potential drugs or vaccines against tuberculosis.
authors.affiliation: Institute of Infection and Immunology, Department of Medical Immunology, Medical School, Anhui University of Science and Technology, Huainan, China. Electronic address: austhudong@126.com.
authors.forename: Dong
authors.initials: D
authors.lastname: Hu
authors.affiliation: Institute of Infection and Immunology, Department of Medical Immunology, Medical School, Anhui University of Science and Technology, Huainan, China. Electronic address: wujing8008@126.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.affiliation: Institute of Infection and Immunology, Department of Medical Immunology, Medical School, Anhui University of Science and Technology, Huainan, China.
authors.forename: Wan
authors.initials: W
authors.lastname: Wang
authors.affiliation: Institute of Infection and Immunology, Department of Medical Immunology, Medical School, Anhui University of Science and Technology, Huainan, China.
authors.forename: Min
authors.initials: M
authors.lastname: Mu
authors.affiliation: Institute of Infection and Immunology, Department of Medical Immunology, Medical School, Anhui University of Science and Technology, Huainan, China.
authors.forename: Runpeng
authors.initials: R
authors.lastname: Zhao
authors.affiliation: Institute of Infection and Immunology, Department of Medical Immunology, Medical School, Anhui University of Science and Technology, Huainan, China.
authors.forename: Xuewei
authors.initials: X
authors.lastname: Xu
authors.affiliation: Institute of Infection and Immunology, Department of Medical Immunology, Medical School, Anhui University of Science and Technology, Huainan, China.
authors.forename: Zhaoquan
authors.initials: Z
authors.lastname: Chen
authors.affiliation: School of Pharmacy, Wenzhou Medical College, Wenzhou, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Xiao
authors.affiliation: Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
authors.forename: Fengyu
authors.initials: F
authors.lastname: Hu
authors.affiliation: Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
authors.forename: Yabo
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Institute of Infection and Immunology, Department of Medical Immunology, Medical School, Anhui University of Science and Technology, Huainan, China. Electronic address: lory456@126.com.
authors.forename: Rongbo
authors.initials: R
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001343:Autophagy; D002460:Cell Line; D054884:Host-Pathogen Interactions; D008247:Lysosomes / Q000378:metabolism* / Q000382:microbiology; D008561:Membrane Fusion; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000201:enzymology* / Q000502:physiology; D010588:Phagosomes / Q000378:metabolism* / Q000382:microbiology; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D014376:Tuberculosis / Q000201:enzymology / Q000378:metabolism / Q000382:microbiology; D037521:Virulence Factors / Q000378:metabolism*; D020691:rab GTP-Binding Proteins / Q000378:metabolism*; D000090802:rab7 GTP-Binding Proteins
chemical_list: D037521:Virulence Factors; D000090802:rab7 GTP-Binding Proteins; C000716465:rab7 GTP-binding proteins, mouse; D010744:Phosphoric Monoester Hydrolases; D020691:rab GTP-Binding Proteins
keywords: Autophagy; Fusion; Lysosome; Rab7; SapM; Tuberculosis