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 Wang1,2, Yan Li1, Xueping Tang2, Xueyi Shang2, Zunquan Zhao3, Yongqiang Jiang3, and Yan Li2* 1
Academy of Military Medical Sciences, Beijing, P. R. China Department of Critical Care Medicine, 5th Medical Center of PLA General Hospital, Beijing, P. R. China 3 State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences Institute of Microbiology and Epidemiology, Beijing, P. R. China 2
(Received May 4, 2020 / Revised Jul 6, 2020 / Accepted Jul 21, 2020)
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. Keywords: Stenotrophomonas maltophilia, OmpA, epithelial, apoptosis, mitochondria
*For correspondence. E-mail: [email protected]; Tel.: +86-10-6694 7371; Fax: +86-10-66947120 § Supplemental material for this article may be found at http://www.springerlink.com/content/120956. Copyright ⓒ 2020, The Microbiological Society of Korea
Introduction Stenotrophomonas maltophilia (S. maltophilia) is a non-fermenting and obligately aerobic Gram-negative bacteria that is widely distributed in nature and resides in the human respiratory tract and feces. It has been well recognised as a common opportunistic pathogen in the clinic (Lee et al., 2014; Li et al., 2017a). Recently, it has been reported that the prevalence of S. maltophilia infection in intensive care units has been increasing continuously (Chang et al., 2012). Outer membrane protein A (OmpA) is a unique protein on the surface or embedded in the cell membrane of Gram-negative bacteria and i
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