Publikation: Neisseria gonorrhoeae Blocks Epithelial Exfoliation by Nitric-Oxide-Mediated Metabolic Cross Talk to Promote Colonization in Mice
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Several pathogens suppress exfoliation, a key defense of epithelia against microbial colonization. Common among these pathogens, exemplified by Neisseria gonorrhoeae, is their ability to bind carcinoembryonic antigen-related cell adhesion molecules (CEACAMs). Gonococcal CEACAM engagement triggers the expression of CD105, which is necessary to block epithelial exfoliation, whereas homotypic CEACAM-CEACAM interactions or antibody-mediated CEACAM clustering does not lead to CD105 expression. Here, we show that CEACAM-associated bacteria release nitric oxide (NO) during anaerobic respiration, and membrane-permeable NO initiates a eukaryotic signaling pathway involving soluble guanylate cyclase (sGC), protein kinase G, and the transcription factor CREB to upregulate CD105 expression. A murine vaginal infection model with N. gonorrhoeae reveals this metabolic cross communication allows bacterial suppression of epithelial exfoliation to facilitate mucosal colonization. Disrupting NO-initiated responses in host cells re-establishes epithelial exfoliation and inhibits mouse genital tract colonization by N. gonorrhoeae, suggesting a host-directed approach to prevent bacterial infections.
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MÜNZNER, Petra, Christof R. HAUCK, 2020. Neisseria gonorrhoeae Blocks Epithelial Exfoliation by Nitric-Oxide-Mediated Metabolic Cross Talk to Promote Colonization in Mice. In: Cell Host & Microbe. Cell Press. 2020, 27(5), pp. 793-808.e5. ISSN 1931-3128. eISSN 1934-6069. Available under: doi: 10.1016/j.chom.2020.03.010BibTex
@article{Munzner2020-05-13Neiss-49823,
year={2020},
doi={10.1016/j.chom.2020.03.010},
title={Neisseria gonorrhoeae Blocks Epithelial Exfoliation by Nitric-Oxide-Mediated Metabolic Cross Talk to Promote Colonization in Mice},
number={5},
volume={27},
issn={1931-3128},
journal={Cell Host & Microbe},
pages={793--808.e5},
author={Münzner, Petra and Hauck, Christof R.}
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<dcterms:abstract xml:lang="eng">Several pathogens suppress exfoliation, a key defense of epithelia against microbial colonization. Common among these pathogens, exemplified by Neisseria gonorrhoeae, is their ability to bind carcinoembryonic antigen-related cell adhesion molecules (CEACAMs). Gonococcal CEACAM engagement triggers the expression of CD105, which is necessary to block epithelial exfoliation, whereas homotypic CEACAM-CEACAM interactions or antibody-mediated CEACAM clustering does not lead to CD105 expression. Here, we show that CEACAM-associated bacteria release nitric oxide (NO) during anaerobic respiration, and membrane-permeable NO initiates a eukaryotic signaling pathway involving soluble guanylate cyclase (sGC), protein kinase G, and the transcription factor CREB to upregulate CD105 expression. A murine vaginal infection model with N. gonorrhoeae reveals this metabolic cross communication allows bacterial suppression of epithelial exfoliation to facilitate mucosal colonization. Disrupting NO-initiated responses in host cells re-establishes epithelial exfoliation and inhibits mouse genital tract colonization by N. gonorrhoeae, suggesting a host-directed approach to prevent bacterial infections.</dcterms:abstract>
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