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.
Highlights
Autophagy is critical for cellular homeostasis [1]
As Neisseria gonorrhoeae (Ngo) is known to interfere with two key components in the autophagic pathway, we determined the influence of this host defense mechanism on the lifecycle of the pathogen
We report that Ngo induces autophagy in human primary cervical epithelial cells as well as endorvical cell lines ME180 and Hec1B
Summary
Conserved from yeast to man, this catabolic process sequesters aging or damaged cytoplasmic contents and organelles in a structure called the autophagosome [2,3,4]. The autophagosome fuses with the lysosome to form the autophagolysosome, where lysosomal enzymes degrade the sequestered contents for recycling [2,3,4]. A double membrane structure called the isolation membrane forms around the cargo targeted for degradation [2, 3]. Initiation of this step requires the class III P(I) kinase VPS34 and Beclin1 [3, 6]. LC3-II plays an important role in cargo selection through binding to adaptor molecules that are associated with damaged cytoplasmic contents [7, 8]
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