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PLoS Pathog. 2017 Apr 13;13(4):e1006269. doi: 10.1371/journal.ppat.1006269. eCollection 2017 Apr.

Neisseria gonorrhoeae infects the human endocervix by activating non-muscle myosin II-mediated epithelial exfoliation.

Author information

1
Department of Cell Biology & Molecular Genetics, University of Maryland, College Park, Maryland, United States of America.
2
Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.
3
Departments of Pathology and Medicine (GI), Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.

Abstract

Colonization and disruption of the epithelium is a major infection mechanism of mucosal pathogens. The epithelium counteracts infection by exfoliating damaged cells while maintaining the mucosal barrier function. The sexually transmitted bacterium Neisseria gonorrhoeae (GC) infects the female reproductive tract primarily from the endocervix, causing gonorrhea. However, the mechanism by which GC overcome the mucosal barrier remains elusive. Using a new human tissue model, we demonstrate that GC can penetrate into the human endocervix by inducing the exfoliation of columnar epithelial cells. We found that GC colonization causes endocervical epithelial cells to shed. The shedding results from the disassembly of the apical junctions that seal the epithelial barrier. Apical junction disruption and epithelial exfoliation increase GC penetration into the endocervical epithelium without reducing bacterial adherence to and invasion into epithelial cells. Both epithelial exfoliation and junction disruption require the activation and accumulation of non-muscle myosin II (NMII) at the apical surface and GC adherent sites. GC inoculation activates NMII by elevating the levels of the cytoplasmic Ca2+ and NMII regulatory light chain phosphorylation. Piliation of GC promotes, but the expression of a GC opacity-associated protein variant, OpaH that binds to the host surface proteins CEACAMs, inhibits GC-induced NMII activation and reorganization and Ca2+ flux. The inhibitory effects of OpaH lead to reductions in junction disruption, epithelial exfoliation, and GC penetration. Therefore, GC phase variation can modulate infection in the human endocervix by manipulating the activity of NMII and epithelial exfoliation.

PMID:
28406994
PMCID:
PMC5391109
DOI:
10.1371/journal.ppat.1006269
[Indexed for MEDLINE]
Free PMC Article

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