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Neisseria gonorrhoeae evades autophagic killing by downregulating CD46-cyt1 and remodeling lysosomes

The Gram-negative human pathogen N. gonorrhoeae (Ngo) quickly attaches to epithelial cells, and large numbers of the bacteria remain on the cell surface for prolonged periods. Ngo invades cells but few viable intracellular bacteria are recovered until later stages of infection, leading to the assump...

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Autores principales: Kim, Won J., Mai, Annette, Weyand, Nathan J., Rendón, Maria A., Van Doorslaer, Koenraad, So, Magdalene
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6388937/
https://www.ncbi.nlm.nih.gov/pubmed/30753248
http://dx.doi.org/10.1371/journal.ppat.1007495
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author Kim, Won J.
Mai, Annette
Weyand, Nathan J.
Rendón, Maria A.
Van Doorslaer, Koenraad
So, Magdalene
author_facet Kim, Won J.
Mai, Annette
Weyand, Nathan J.
Rendón, Maria A.
Van Doorslaer, Koenraad
So, Magdalene
author_sort Kim, Won J.
collection PubMed
description The Gram-negative human pathogen N. gonorrhoeae (Ngo) quickly attaches to epithelial cells, and large numbers of the bacteria remain on the cell surface for prolonged periods. Ngo invades cells but few viable intracellular bacteria are recovered until later stages of infection, leading to the assumption that Ngo is a weak invader. On the cell surface, Ngo quickly recruits CD46-cyt1 to the epithelial cell cortex directly beneath the bacteria and causes its cleavage by metalloproteinases and Presenilin/γSecretease; how these interactions affect the Ngo lifecycle is unknown. Here, we show Ngo induces an autophagic response in the epithelial cell through CD46-cyt1/GOPC, and this response kills early invaders. Throughout infection, the pathogen slowly downregulates CD46-cyt1 and remodeling of lysosomes, another key autophagy component, and these activities ultimately promote intracellular survival. We present a model on the dynamics of Ngo infection and describe how this dual interference with the autophagic pathway allows late invaders to survive within the cell.
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spelling pubmed-63889372019-03-08 Neisseria gonorrhoeae evades autophagic killing by downregulating CD46-cyt1 and remodeling lysosomes Kim, Won J. Mai, Annette Weyand, Nathan J. Rendón, Maria A. Van Doorslaer, Koenraad So, Magdalene PLoS Pathog Research Article The Gram-negative human pathogen N. gonorrhoeae (Ngo) quickly attaches to epithelial cells, and large numbers of the bacteria remain on the cell surface for prolonged periods. Ngo invades cells but few viable intracellular bacteria are recovered until later stages of infection, leading to the assumption that Ngo is a weak invader. On the cell surface, Ngo quickly recruits CD46-cyt1 to the epithelial cell cortex directly beneath the bacteria and causes its cleavage by metalloproteinases and Presenilin/γSecretease; how these interactions affect the Ngo lifecycle is unknown. Here, we show Ngo induces an autophagic response in the epithelial cell through CD46-cyt1/GOPC, and this response kills early invaders. Throughout infection, the pathogen slowly downregulates CD46-cyt1 and remodeling of lysosomes, another key autophagy component, and these activities ultimately promote intracellular survival. We present a model on the dynamics of Ngo infection and describe how this dual interference with the autophagic pathway allows late invaders to survive within the cell. Public Library of Science 2019-02-12 /pmc/articles/PMC6388937/ /pubmed/30753248 http://dx.doi.org/10.1371/journal.ppat.1007495 Text en © 2019 Kim et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Kim, Won J.
Mai, Annette
Weyand, Nathan J.
Rendón, Maria A.
Van Doorslaer, Koenraad
So, Magdalene
Neisseria gonorrhoeae evades autophagic killing by downregulating CD46-cyt1 and remodeling lysosomes
title Neisseria gonorrhoeae evades autophagic killing by downregulating CD46-cyt1 and remodeling lysosomes
title_full Neisseria gonorrhoeae evades autophagic killing by downregulating CD46-cyt1 and remodeling lysosomes
title_fullStr Neisseria gonorrhoeae evades autophagic killing by downregulating CD46-cyt1 and remodeling lysosomes
title_full_unstemmed Neisseria gonorrhoeae evades autophagic killing by downregulating CD46-cyt1 and remodeling lysosomes
title_short Neisseria gonorrhoeae evades autophagic killing by downregulating CD46-cyt1 and remodeling lysosomes
title_sort neisseria gonorrhoeae evades autophagic killing by downregulating cd46-cyt1 and remodeling lysosomes
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6388937/
https://www.ncbi.nlm.nih.gov/pubmed/30753248
http://dx.doi.org/10.1371/journal.ppat.1007495
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