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Restriction endonucleases from invasive Neisseria gonorrhoeae cause double-strand breaks and distort mitosis in epithelial cells during infection
Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
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(English)Manuscript (preprint) (Other academic)
Keyword [en]
Restriction endonucleases, N. gonorrhoeae, VK2E6/E7 cells, mitosis
National Category
Microbiology
Research subject
Microbiology; Infectious Diseases
Identifiers
URN: urn:nbn:se:su:diva-107688OAI: oai:DiVA.org:su-107688DiVA: diva2:749521
Available from: 2014-09-24 Created: 2014-09-24 Last updated: 2014-09-29
In thesis
1. Host epithelium integrity in the female reproductive tract during Neisseria gonorrhoeae infection
Open this publication in new window or tab >>Host epithelium integrity in the female reproductive tract during Neisseria gonorrhoeae infection
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Neisseria gonorrhoeae infections are asymptomatic in approximately fifty percent of the affected women. Left untreated, this can develop into a long-term inflammatory state with detrimental secondary complications such as ectopic pregnancy and sterility. Furthermore, studies have shown that N. gonorrhoeae infection may be a contributing factor to urogenital cancers.

We found that gonococcal infections induce DNA damage in human vaginal and cervical cells. As a consequence of the DNA damage the cell cycle progression is altered. Mitotic checkpoint genes and proteins important in regulation of metaphase were distorted. Partly because of this, the progression of mitosis was hampered. An additional contributing cause of the DNA damage and dysfunctional mitosis is the release of endogenous gonococcal restriction endonucleases.

Most N. gonorrhoeae infection studies are performed on cultured monolayers of cells derived from tumors.  In order to create a system which more resembled in vivo conditions and study N. gonorrhoeae infections, we developed a polarized epithelium of human non-tumorigenic vaginal VK2/E6E7 cells. In the search for an animal model for the human-restricted pathogen we evaluated the CD46 transgenic mouse model in the study of gonococcal infections.

In summary, this thesis aims to increase the understanding of the basic molecular function of how invasive gonococcal infections affect host cell cycle regulation, DNA integrity and potential predisposition to cellular malignancies in the epithelium of the female reproductive tract. Since the female reproductive tract is colonized with Lactobacillus, the impact of lactobacilli to the host cell cycle has also been investigated.

Place, publisher, year, edition, pages
Stockholm: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, 2014. 64 p.
Keyword
Female reproductive tract, Neisseria gonorrhoeae, VK2/E6E7 cells, DNA damage, cell cycle, mitosis, restriction endonucleases, infection models
National Category
Microbiology
Research subject
Molecular Bioscience
Identifiers
urn:nbn:se:su:diva-107713 (URN)978-91-7649-007-5 (ISBN)
Public defence
2014-11-07, Nordenskiöldsalen, Geovetenskapens hus, Svante Arrheniusväg 12, Stockholm, 10:00 (English)
Opponent
Supervisors
Note

At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 3: Manuscript. Paper 4: Manuscript. Paper 5: Manuscript.

Available from: 2014-10-16 Created: 2014-09-24 Last updated: 2014-11-21Bibliographically approved

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