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. 2020 Sep 2;58(10):868–877. doi: 10.1007/s12275-020-0235-9

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,✉
PMCID: PMC7463227  PMID: 32876914

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 mi-tochondrial pathways.

Electronic Supplementary Material

Supplementary material is available for this article at 10.1007/s12275-020-0235-9 and is accessible for authorized users.

Keywords: Stenotrophomonas maltophilia, OmpA, epithelial, apoptosis, mitochondria

Electronic Supplementary Material

12275_2020_235_MOESM1_ESM.pdf (202KB, pdf)

Supplementary material, approximately 201 KB.

Acknowledgments

This work was supported by the National Natural Science Foundation of China (81571959, 81071399). The funder had no role in study design, data collectionand analysis, decision to publish, or preparation of the manuscript.

Footnotes

Supplemental material for this article may be found at http://www.springerlink.com/content/120956.

Conflict of Interest

The authors declare that they have no competing interests.

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