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OmpA of Klebsiella pneumoniae ATCC 13883 induces pyroptosis in HEp-2 cells, leading to cell-cycle arrest and apoptosis.
- Source :
-
Microbes and infection [Microbes Infect] 2020 Oct; Vol. 22 (9), pp. 432-440. Date of Electronic Publication: 2020 Jun 19. - Publication Year :
- 2020
-
Abstract
- Klebsiella pneumoniae is an opportunistic pathogenic bacterium that commonly causes pneumonia in elderly people. OmpA, a toxin that is highly expressed in the outer membrane of the bacterium, is one of the primary factors implicated in the pulmonary pathogenesis of K. pneumoniae. To evaluate the associated pyroptosis mechanism of infection, the ompA gene was cloned, and the protein was expressed, extracted, and used to treat human larynx epithelial cells. We observed that OmpA induces reactive oxygen species production and cell-cycle arrest in the G2/M phase in host cells, leading to subsequent apoptosis. Moreover, OmpA was found to induce IL-1β and IL-18 production in host cells, resulting in caspase-1 activation, which simultaneously stimulated pyroptosis, thus leading to the death of the host cells. We next sought to examine differential gene expression via RNA sequencing to better elucidate the mechanisms associated with these cellular changes, and found that genes associated with these pathways were more highly expressed in OmpA-treated cells than in K. pneumoniae-infected cells. Thus, cell-cycle arrest, apoptosis, and pyroptosis may serve as the primary defenses employed by host cells against OmpA. These results provide novel insights into the host defense against K. pneumoniae infection.<br />Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest (commercial or otherwise) to declare regarding this study.<br /> (Copyright © 2020 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)
- Subjects :
- Bacterial Outer Membrane Proteins genetics
Bacterial Toxins genetics
Caspase 1
Cell Cycle
Cell Line
Cytokines metabolism
Epithelial Cells
Genes, Bacterial genetics
Humans
Interleukin-18
Interleukin-1beta
Klebsiella pneumoniae genetics
Lung
Pneumonia
Reactive Oxygen Species metabolism
Apoptosis
Bacterial Outer Membrane Proteins metabolism
Cell Cycle Checkpoints physiology
Host-Pathogen Interactions physiology
Klebsiella Infections microbiology
Klebsiella pneumoniae metabolism
Pyroptosis
Subjects
Details
- Language :
- English
- ISSN :
- 1769-714X
- Volume :
- 22
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Microbes and infection
- Publication Type :
- Academic Journal
- Accession number :
- 32569734
- Full Text :
- https://doi.org/10.1016/j.micinf.2020.06.002