2. Academic Validation
  3. Outer membrane protein a in Acinetobacter baumannii induces autophagy through mTOR signalling pathways in the lung of SD rats

Outer membrane protein a in Acinetobacter baumannii induces autophagy through mTOR signalling pathways in the lung of SD rats

  • Biomed Pharmacother. 2021 Mar;135:111034. doi: 10.1016/j.biopha.2020.111034.
Dan Zhao 1,  Yumei Li 2,  Chunhong Peng 3,  Jieru Lin 1,  Fuxun Yu 4,  Yichen Zhao 5,  Xiangyan Zhang 3,  Degang Zhao 6
Affiliations

Affiliations

  • 1 College of Life Sciences, Guizhou University, Guiyang 550025, PR China; Department of Respiratory and Critical Care Medicine, Guizhou Provincial People's Hospital, Guiyang 550002, PR China; NHC Key Laboratory of Pulmonary Immunological Diseases, The People's Hospital Guizhou University, Guiyang 550002, PR China.
  • 2 Department of Anatomy, Guizhou Medical University, Guiyang 550025, PR China.
  • 3 Department of Respiratory and Critical Care Medicine, Guizhou Provincial People's Hospital, Guiyang 550002, PR China; NHC Key Laboratory of Pulmonary Immunological Diseases, The People's Hospital Guizhou University, Guiyang 550002, PR China.
  • 4 NHC Key Laboratory of Pulmonary Immunological Diseases, The People's Hospital Guizhou University, Guiyang 550002, PR China; Department of Central Laboratory, Guizhou Provincial People's Hospital, Guiyang 550002, PR China.
  • 5 College of Life Sciences, Guizhou University, Guiyang 550025, PR China; Institute of Biological Engineering, Guizhou University, Guiyang 550025, PR China.
  • 6 College of Life Sciences, Guizhou University, Guiyang 550025, PR China; Institute of Biological Engineering, Guizhou University, Guiyang 550025, PR China. Electronic address: dgzhao@gzu.edu.cn.
PMID: 33388597 DOI: 10.1016/j.biopha.2020.111034
Abstract

Outer membrane protein A (OmpA) of Acinetobacter baumannii (A. baumannii) is associated with Autophagy, which plays an important role in its pathogenicity. However, its exact pathophysiological role in the process of lung tissue cell Autophagy remains unclear. In this study, animal and cell Infection models were established by wild A. baumannii strain and An OmpA knockout mutant (OmpA-/- A. baumannii) strain. The expression levels of markers Autophagy, histological change, cell viability and protein expression levels of inflammatory cytokines were examined. OmpA-/-A. baumannii was successfully constructed. The capacities of Bacterial adhesion and invasion to host cells increased more obviously in the AB group and the AB + Rapa group than in the OmpA-/- AB group and AB + CQ group. The AB group and AB + Rapa group could produce double membrane vacuoles, endoplasmic reticulum dilation, mitochondrial ridge rupture, and mitochondrial vacuoles. OmpA could lead to increased LC3, AMPK, and PAMPK protein release, and decreased levels of p62, mTOR and pmTOR proteins in vivo and in vitro. OmpA caused lung pathology and the release of inflammatory cytokines. A. baumannii OmpA promotes Autophagy in lung cells through the mTOR signalling pathway, which increases the Bacterial colonization ability in the double-layer membrane autophagosome formed by the Autophagy reaction to escape the clearance of bacteria by the host, promote the release of inflammatory mediators and aggravate the damage to the host.

Keywords

Acinetobacter baumannii; Autophagy; Lung cell; Outer membrane protein A; mTOR signalling pathway.

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