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Folliculin Controls the Intracellular Survival and Trans-Epithelial Passage of Neisseria gonorrhoeae

Neisseria gonorrhoeae, a Gram-negative obligate human pathogenic bacterium, infects human epithelial cells and causes sexually transmitted diseases. Emerging multi-antibiotic resistant gonococci and increasing numbers of infections complicate the treatment of infected patients. Here, we used an shRN...

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Autores principales: Yang, Tao, Heydarian, Motaharehsadat, Kozjak-Pavlovic, Vera, Urban, Manuela, Harbottle, Richard P., Rudel, Thomas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7499807/
https://www.ncbi.nlm.nih.gov/pubmed/33014885
http://dx.doi.org/10.3389/fcimb.2020.00422
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author Yang, Tao
Heydarian, Motaharehsadat
Kozjak-Pavlovic, Vera
Urban, Manuela
Harbottle, Richard P.
Rudel, Thomas
author_facet Yang, Tao
Heydarian, Motaharehsadat
Kozjak-Pavlovic, Vera
Urban, Manuela
Harbottle, Richard P.
Rudel, Thomas
author_sort Yang, Tao
collection PubMed
description Neisseria gonorrhoeae, a Gram-negative obligate human pathogenic bacterium, infects human epithelial cells and causes sexually transmitted diseases. Emerging multi-antibiotic resistant gonococci and increasing numbers of infections complicate the treatment of infected patients. Here, we used an shRNA library screen and next-generation sequencing to identify factors involved in epithelial cell infection. Folliculin (FLCN), a 64 kDa protein with a tumor repressor function was identified as a novel host factor important for N. gonorrhoeae survival after uptake. We further determined that FLCN did not affect N. gonorrhoeae adherence and invasion but was essential for its survival in the cells by modulating autophagy. In addition, FLCN was also required to maintain cell to cell contacts in the epithelial layer. In an infection model with polarized cells, FLCN inhibited the polarized localization of E-cadherin and the transcytosis of gonococci across polarized epithelial cells. In conclusion, we demonstrate here the connection between FLCN and bacterial infection and in particular the role of FLCN in the intracellular survival and transcytosis of gonococci across polarized epithelial cell layers.
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spelling pubmed-74998072020-10-02 Folliculin Controls the Intracellular Survival and Trans-Epithelial Passage of Neisseria gonorrhoeae Yang, Tao Heydarian, Motaharehsadat Kozjak-Pavlovic, Vera Urban, Manuela Harbottle, Richard P. Rudel, Thomas Front Cell Infect Microbiol Cellular and Infection Microbiology Neisseria gonorrhoeae, a Gram-negative obligate human pathogenic bacterium, infects human epithelial cells and causes sexually transmitted diseases. Emerging multi-antibiotic resistant gonococci and increasing numbers of infections complicate the treatment of infected patients. Here, we used an shRNA library screen and next-generation sequencing to identify factors involved in epithelial cell infection. Folliculin (FLCN), a 64 kDa protein with a tumor repressor function was identified as a novel host factor important for N. gonorrhoeae survival after uptake. We further determined that FLCN did not affect N. gonorrhoeae adherence and invasion but was essential for its survival in the cells by modulating autophagy. In addition, FLCN was also required to maintain cell to cell contacts in the epithelial layer. In an infection model with polarized cells, FLCN inhibited the polarized localization of E-cadherin and the transcytosis of gonococci across polarized epithelial cells. In conclusion, we demonstrate here the connection between FLCN and bacterial infection and in particular the role of FLCN in the intracellular survival and transcytosis of gonococci across polarized epithelial cell layers. Frontiers Media S.A. 2020-09-04 /pmc/articles/PMC7499807/ /pubmed/33014885 http://dx.doi.org/10.3389/fcimb.2020.00422 Text en Copyright © 2020 Yang, Heydarian, Kozjak-Pavlovic, Urban, Harbottle and Rudel. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cellular and Infection Microbiology
Yang, Tao
Heydarian, Motaharehsadat
Kozjak-Pavlovic, Vera
Urban, Manuela
Harbottle, Richard P.
Rudel, Thomas
Folliculin Controls the Intracellular Survival and Trans-Epithelial Passage of Neisseria gonorrhoeae
title Folliculin Controls the Intracellular Survival and Trans-Epithelial Passage of Neisseria gonorrhoeae
title_full Folliculin Controls the Intracellular Survival and Trans-Epithelial Passage of Neisseria gonorrhoeae
title_fullStr Folliculin Controls the Intracellular Survival and Trans-Epithelial Passage of Neisseria gonorrhoeae
title_full_unstemmed Folliculin Controls the Intracellular Survival and Trans-Epithelial Passage of Neisseria gonorrhoeae
title_short Folliculin Controls the Intracellular Survival and Trans-Epithelial Passage of Neisseria gonorrhoeae
title_sort folliculin controls the intracellular survival and trans-epithelial passage of neisseria gonorrhoeae
topic Cellular and Infection Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7499807/
https://www.ncbi.nlm.nih.gov/pubmed/33014885
http://dx.doi.org/10.3389/fcimb.2020.00422
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