Kuo-Yang Huang1, Ruei-Min Chen2, Hsin-Chung Lin3, Wei-Hung Cheng4, Hsin-An Lin5, Wei-Ning Lin6, Po-Jung Huang7, Cheng-Hsun Chiu8, Petrus Tang9. 1. Graduate Institute of Pathology and Parasitology, National Defense Medical Center, Taipei City, Taiwan. 2. Division of Clinical Pathology, Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei City, Taiwan. 3. Division of Clinical Pathology, Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei City, Taiwan; Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei City, Taiwan. 4. Molecular Regulation and Bioinformatics Laboratory, Department of Parasitology, College of Medicine, Chang Gung University, Taoyuan City, Taiwan. 5. Division of Infection, Department of Medicine, Tri-Service General Hospital SongShan Branch, Taipei City, Taiwan. 6. Graduate Institute of Biomedical and Pharmaceutical Science, Fu Jen Catholic University, New Taipei City, Taiwan. 7. Department of Biomedical Sciences, Chang Gung University, Taoyuan City, Taiwan; Genomic Medicine Core Laboratory, Chang Gung Memorial Hospital, Linkou, Taiwan. 8. Molecular Infectious Diseases Research Center, Chang Gung Memorial Hospital, Taoyuan City, Taiwan. 9. Molecular Regulation and Bioinformatics Laboratory, Department of Parasitology, College of Medicine, Chang Gung University, Taoyuan City, Taiwan; Molecular Infectious Diseases Research Center, Chang Gung Memorial Hospital, Taoyuan City, Taiwan. Electronic address: petang@mail.cgu.edu.tw.
Abstract
BACKGROUND: Autophagy has been shown to be involved in the pathogenesis of several protists, offering prospects for the developments of new drugs targeting autophagy. However, there is no evidence illustrating functional autophagy in the deep-branching trichomonads. The human parasitic protist Trichomonas vaginalis has been predicted to possess reduced autophagic machinery, with only autophagy-related protein 8 (Atg8) conjugation system required for autophagosome formation. METHODS: The recombinant protein of TvAtg8 (rTvAtg8) and the polyclonal antibody against rTvAtg8 were generated. The expression and localization of TvAtg8 was monitored upon autophagy induction by glucose restriction (GR) compared with glucose-rich cultivation. The role of TvAtg8 in proteolysis was clarified. RESULTS: Here, we report that T. vaginalis Atg8 (TvAtg8) is upregulated and conjugated to autophagosome-like vesicles upon autophagy induction by GR. Moreover, we investigate, for the first time, the role of autophagy in T. vaginalis. Proteasome inhibition (PI)-induced autophagy compensates for the removal of polyubiquitinated proteins under glucose-rich condition. GR-induced autophagy is a major proteolytic system in T. vaginalis. These results suggest that autophagy is vital for proteolysis in T. vaginalis with an impaired ubiquitin-proteasome system or under glucose-limited environment. CONCLUSION: Our findings unveiled previously unidentified functions of autophagy in proteostasis in trichomonads, advancing our understanding of this highly conserved process in the ancient eukaryote.
BACKGROUND: Autophagy has been shown to be involved in the pathogenesis of several protists, offering prospects for the developments of new drugs targeting autophagy. However, there is no evidence illustrating functional autophagy in the deep-branching trichomonads. The human parasitic protist Trichomonas vaginalis has been predicted to possess reduced autophagic machinery, with only autophagy-related protein 8 (Atg8) conjugation system required for autophagosome formation. METHODS: The recombinant protein of TvAtg8 (rTvAtg8) and the polyclonal antibody against rTvAtg8 were generated. The expression and localization of TvAtg8 was monitored upon autophagy induction by glucose restriction (GR) compared with glucose-rich cultivation. The role of TvAtg8 in proteolysis was clarified. RESULTS: Here, we report that T. vaginalis Atg8 (TvAtg8) is upregulated and conjugated to autophagosome-like vesicles upon autophagy induction by GR. Moreover, we investigate, for the first time, the role of autophagy in T. vaginalis. Proteasome inhibition (PI)-induced autophagy compensates for the removal of polyubiquitinated proteins under glucose-rich condition. GR-induced autophagy is a major proteolytic system in T. vaginalis. These results suggest that autophagy is vital for proteolysis in T. vaginalis with an impaired ubiquitin-proteasome system or under glucose-limited environment. CONCLUSION: Our findings unveiled previously unidentified functions of autophagy in proteostasis in trichomonads, advancing our understanding of this highly conserved process in the ancient eukaryote.
Authors: Anthony J O'Donoghue; Betsaida Bibo-Verdugo; Yukiko Miyamoto; Steven C Wang; Justin Z Yang; Douglas E Zuill; Shoun Matsuka; Zhenze Jiang; Jehad Almaliti; Conor R Caffrey; William H Gerwick; Lars Eckmann Journal: Antimicrob Agents Chemother Date: 2019-10-22 Impact factor: 5.191
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