Title |
Stenotrophomonas maltophilia outer membrane protein A induces epithelial cell apoptosis via mitochondrial pathways |
Author |
Xin Wang1,2, Yan Li1, Xueping Tang2, Xueyi Shang2, Zunquan Zhao3, Yongqiang Jiang3, and Yan Li2* |
Address |
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. China |
Bibliography |
Journal of Microbiology, 58(10),868–877, 2020,
|
DOI |
10.1007/s12275-020-0235-9
|
Key Words |
Stenotrophomonas maltophilia, OmpA, epithelial,
apoptosis, mitochondria |
Abstract |
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. |