Neisseria gonorrhoeae evades autophagic killing by downregulating CD46-cyt1 and remodeling lysosomes
AffiliationUniv Arizona, BIO5 Inst
Univ Arizona, Dept Immunobiol
Univ Arizona, Sch Anim & Comparat Biomed Sci
MetadataShow full item record
PublisherPUBLIC LIBRARY SCIENCE
CitationKim WJ, Mai A, Weyand NJ, Rendón MA, Van Doorslaer K, So M (2019) Neisseria gonorrhoeae evades autophagic killing by downregulating CD46-cyt1 and remodeling lysosomes. PLoS Pathog 15(2): e1007495. https://doi.org/10.1371/journal.ppat.1007495
Rights© 2019 Kim et al. This is an open access article distributed under the terms of the Creative Commons Attribution License
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AbstractThe 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/Secretease; 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. Author summary Neisseria gonorrhoeae (Ngo), which causes the sexually transmitted disease of gonorrhea, primarily infects the uorgenital epithelium. It attaches to the epithelial surface for lengthy periods. It also invades epithelial cells, but few viable intracellular bacteria are recovered until later stages of infection. As 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. Autophagy is induced through the CD46-cyt1/GOPC pathway and this response kills Ngo invading cells early in infection. Throughout infection, Ngo mounts a counter-attack on the autophagic pathway by downregulating CD46-cyt1 and disturbing lysosome homeostasis. This interference allows late-invading Ngo to escape autophagic killing.
NoteOpen access journal
VersionFinal published version
SponsorsNational Institute of Allergy and Infectious Disease [R01 AI081972]
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