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PLoS Pathog. 2019 Feb 12;15(2):e1007495. doi: 10.1371/journal.ppat.1007495. eCollection 2019 Feb.

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

Author information

1
BIO5 Institute, University of Arizona, Tucson, AZ, United States of America.
2
Department of Immunobiology, University of Arizona, Tucson, AZ, United States of America.
3
Department of Biological Sciences, Ohio University, Athens, OH, United States of America.
4
School of Animal and Comparative Biomedical Sciences, University of Arizona, Tucson, AZ, United States of America.

Abstract

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.

PMID:
30753248
PMCID:
PMC6388937
DOI:
10.1371/journal.ppat.1007495
[Indexed for MEDLINE]
Free PMC Article

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