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...

Full description

Saved in:
Bibliographic Details
Published in:PLoS pathogens 2019-02, Vol.15 (2), p.e1007495-e1007495
Main Authors: Kim, Won J, Mai, Annette, Weyand, Nathan J, Rendón, Maria A, Van Doorslaer, Koenraad, So, Magdalene
Format: Article
Language:English
Subjects:
Antigens
Autophagy
Autophagy (Cytology)
Autophagy - physiology
Bacteria
Bacterial Adhesion
Biology and Life Sciences
CD46 antigen
Cell death
Cell Line
Cell surface
Cellular signal transduction
Cervix Uteri
Down-Regulation
Epithelial Cells
Female
Fimbriae, Bacterial
Genetic aspects
Gonorrhea - metabolism
Gonorrhea - physiopathology
Homeostasis
Humans
Infection
Infections
Intracellular
Life cycle analysis
Lysosomes
Measles
Medicine and Health Sciences
Membrane Cofactor Protein - immunology
Membrane Cofactor Protein - physiology
Membrane Glycoproteins
Membrane proteins
Membrane Proteins - metabolism
Neisseria gonorrhoeae
Neisseria gonorrhoeae - metabolism
Neisseria gonorrhoeae - pathogenicity
Pathogens
Phagocytosis
Presenilin
Primary Cell Culture
Protein Isoforms
Proteins
Research and Analysis Methods
Salmonella
Supervision
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1553-7374
1553-7366
1553-7374
DOI:10.1371/journal.ppat.1007495