title: The Pseudomonas aeruginosa Type VI Secretion PGAP1-like Effector Induces Host Autophagy by Activating Endoplasmic Reticulum Stress.
abstract: Pseudomonas aeruginosa is an opportunistic pathogen that regularly causes nosocomial infections in hospitalized patients. The type VI secretion system (T6SS) is responsible for the secretion of numerous virulence effector proteins that can both interfere with competing microbes and manipulate host cells. Here, we report a detailed investigation of a P. aeruginosa H2-T6SS-dependent phospholipase effector, TplE, which acts as a trans-kingdom toxin. Delivery of TplE to the periplasmic space of rival bacteria leads to growth inhibition. Importantly, TplE, also contains a eukaryotic PGAP1-like domain, which targets the host ER apparatus, ultimately leading to disruption of the ER. TplE activity leads to the activation of the unfolded protein response (UPR) through the IRE1α-XBP1 pathway, enhancing autophagic flux. These findings indicate that this T6SS-delivered phospholipase effector is active against both prokaryotic and eukaryotic cellular targets, highlighting the T6SS as a versatile weapon in the Pseudomonas arsenal.
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, 6 Rong Jing Dong Jie, Beijing 100176, P.R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Jiang
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, 6 Rong Jing Dong Jie, Beijing 100176, P.R. China.
authors.forename: Xia
authors.initials: X
authors.lastname: Wang
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, 6 Rong Jing Dong Jie, Beijing 100176, P.R. China.
authors.forename: Bei
authors.initials: B
authors.lastname: Wang
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, 6 Rong Jing Dong Jie, Beijing 100176, P.R. China.
authors.forename: Lihong
authors.initials: L
authors.lastname: Chen
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, 6 Rong Jing Dong Jie, Beijing 100176, P.R. China.
authors.forename: Zhendong
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Division of Biomedical Science, Warwick Medical School, Warwick University, Coventry CV4 7AL, UK.
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Waterfield
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, 6 Rong Jing Dong Jie, Beijing 100176, P.R. China. Electronic address: yangguowei@hotmail.com.
authors.forename: Guowei
authors.initials: G
authors.lastname: Yang
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, 6 Rong Jing Dong Jie, Beijing 100176, P.R. China. Electronic address: zdsys@vip.sina.com.
authors.forename: Qi
authors.initials: Q
authors.lastname: Jin
mesh_terms: D000818:Animals; D001343:Autophagy / Q000502:physiology*; D001426:Bacterial Proteins / Q000378:metabolism; D058947:Bacterial Secretion Systems / Q000378:metabolism; D003428:Cross Infection / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress / Q000502:physiology*; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D011550:Pseudomonas aeruginosa / Q000378:metabolism*; D000069376:Type VI Secretion Systems / Q000378:metabolism*; D014774:Virulence / Q000502:physiology
chemical_list: D001426:Bacterial Proteins; D058947:Bacterial Secretion Systems; D008565:Membrane Proteins; D000069376:Type VI Secretion Systems; C484857:PGAP1 protein, human; D010744:Phosphoric Monoester Hydrolases