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Stenotrophomonas maltophilia outer membrane protein A induces epithelial cell apoptosis via mitochondrial pathways
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Stenotrophomonas maltophilia outer membrane protein A induces epithelial cell apoptosis via mitochondrial pathways
Xin Wang 1,2, Yan Li 1, Xueping Tang 2, Xueyi Shang 2, Zunquan Zhao 3, Yongqiang Jiang 3, Yan Li 2
Journal of Microbiology 2020;58(10):868-877
DOI: https://doi.org/10.1007/s12275-020-0235-9
Published online: September 2, 2020
1Academy of Military Medical Sciences, Beijing, P. R. China, 2Department of Critical Care Medicine, 5th Medical Center of PLA General Hospital, Beijing, P. R. China, 3State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences Institute of Microbiology and Epidemiology, Beijing, P. R. China1Academy of Military Medical Sciences, Beijing, P. R. China, 2Department of Critical Care Medicine, 5th Medical Center of PLA General Hospital, Beijing, P. R. China, 3State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences Institute of Microbiology and Epidemiology, Beijing, P. R. China
Corresponding author:  Yan Li , Tel: +86-10-6694-7371, 
Received: 4 May 2020   • Revised: 6 July 2020   • Accepted: 21 July 2020
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Stenotrophomonas maltophilia (S. maltophilia) is a common opportunistic pathogen in intensive care units and causes infections most often after surgeries in immune-compromised patients such as those undergoing chemotherapy. Outer membrane protein A (OmpA) is the most abundant of the outer membrane proteins in S. maltophilia. Previous studies on OmpA usually focus on its interaction with the host cells and its role in vaccine development. However, the impact of OmpA on the virulence of S. maltophilia to host cells and the effects on apoptosis remain unclear. In this study, we exposed purified recombinant S. maltophilia OmpA (rOmpA) to HEp-2 cells and investigated the effects of OmpA on epithelial cell apoptosis. Morphologic and flow cytometric analyses revealed that HEp-2 cells stimulated with rOmpA multiple apoptosis features, including nuclear roundness and pyknosis, chromatin aggregation, and phosphatidylserine eversion. We found that rOmpA regulated the protein levels of Bax and Bcl-xL in HEp-2 cells, leading to changes in mitochondria permeability and the release of cytochrome c and apoptosis-inducing factors into the cytoplasm. These subsequently activate the caspase-9/caspase-3 pathway that promote apoptosis. We also observed that rOmpA enhanced the generation of reactive oxygen species and increased intracellular Ca2+ levels in HEp-2 cells. Collectively, our data suggested that rOmpA induced epithelial cells apoptosis via mitochondrial pathways.

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    Stenotrophomonas maltophilia outer membrane protein A induces epithelial cell apoptosis via mitochondrial pathways
    J. Microbiol. 2020;58(10):868-877.   Published online September 2, 2020
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