title: Critical role of bacterial isochorismatase in the autophagic process induced by Acinetobacter baumannii in mammalian cells.
abstract: A recent study reported that Acinetobacter baumannii could induce autophagy, but the recognition and clearance mechanism of intracytosolic A. baumannii in the autophagic process and the molecular mechanism of autophagy induced by the pathogen remains unknown. In this study, we first demonstrated that invading A. baumannii induced a complete, ubiquitin-mediated autophagic response that is dependent upon septins SEPT2 and SEPT9 in mammalian cells. We also demonstrated that autophagy induced by A. baumannii was Beclin-1 dependent via the AMPK/ERK/mammalian target of rapamycin pathway. Of interest, we found that the isochorismatase mutant strain had significantly decreased siderophore-mediated ferric iron acquisition ability and had a reduced the ability to induce autophagy. We verified that isochorismatase was required for the recognition of intracytosolic A. baumannii mediated by septin cages, ubiquitinated proteins, and ubiquitin-binding adaptor proteins p62 and NDP52 in autophagic response. We also confirmed that isochorismatase was required for the clearance of invading A. baumannii by autophagy in vitro and in the mouse model of infection. Together, these findings provide insight into the distinctive recognition and clearance of intracytosolic A. baumannii by autophagy in host cells, and that isochorismatase plays a critical role in the A. baumannii-induced autophagic process.-Wang, Y., Zhang, K., Shi, X., Wang, C., Wang, F., Fan, J., Shen, F., Xu, J., Bao, W., Liu, M., Yu, L. Critical role of bacterial isochorismatase in the autophagic process induced by Acinetobacter baumannii in mammalian cells.
authors.affiliation: Department of Infectious Diseases, First Hospital of Jilin University, Key Laboratory for Zoonosis Research, Institute of Zoonosis, Ministry of Medical Sciences, Changchun, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Infectious Diseases, First Hospital of Jilin University, Key Laboratory for Zoonosis Research, Institute of Zoonosis, Ministry of Medical Sciences, Changchun, China.
authors.forename: Kaiyu
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Infectious Diseases, First Hospital of Jilin University, Key Laboratory for Zoonosis Research, Institute of Zoonosis, Ministry of Medical Sciences, Changchun, China.
authors.forename: Xiaochen
authors.initials: X
authors.lastname: Shi
authors.affiliation: Department of Infectious Diseases, First Hospital of Jilin University, Key Laboratory for Zoonosis Research, Institute of Zoonosis, Ministry of Medical Sciences, Changchun, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Infectious Diseases, First Hospital of Jilin University, Key Laboratory for Zoonosis Research, Institute of Zoonosis, Ministry of Medical Sciences, Changchun, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: Laboratory Animal Center, Academy of Military Medical Sciences, Beijing, China.
authors.forename: Junwen
authors.initials: J
authors.lastname: Fan
authors.affiliation: Department of Infectious Diseases, First Hospital of Jilin University, Key Laboratory for Zoonosis Research, Institute of Zoonosis, Ministry of Medical Sciences, Changchun, China; Jiangsu Co-innovation Center for the Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, China.
authors.forename: Fengge
authors.initials: F
authors.lastname: Shen
authors.affiliation: College of Veterinary Medicine and Animal Science, Jilin University, Changchun, China.
authors.forename: Jiancheng
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Infectious Diseases, First Hospital of Jilin University, Key Laboratory for Zoonosis Research, Institute of Zoonosis, Ministry of Medical Sciences, Changchun, China.
authors.forename: Wanguo
authors.initials: W
authors.lastname: Bao
authors.affiliation: Department of Infectious Diseases, First Hospital of Jilin University, Key Laboratory for Zoonosis Research, Institute of Zoonosis, Ministry of Medical Sciences, Changchun, China; Department of Clinical Laboratory, First Hospital of Jilin University, Changchun, China; and.
authors.forename: Mingyuan
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Infectious Diseases, First Hospital of Jilin University, Key Laboratory for Zoonosis Research, Institute of Zoonosis, Ministry of Medical Sciences, Changchun, China; Jiangsu Co-innovation Center for the Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, China yu_lu@jlu.edu.cn.
authors.forename: Lu
authors.initials: L
authors.lastname: Yu
mesh_terms: D040981:Acinetobacter baumannii / Q000201:enzymology*; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D001343:Autophagy / Q000502:physiology*; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000378:metabolism; D006801:Humans; D006867:Hydrolases / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008807:Mice, Inbred BALB C; D025801:Ubiquitin / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D025801:Ubiquitin; D006867:Hydrolases; C064012:isochorismatase
keywords: bacteria clearance; pathway; septin