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P orphyromonas gingivalis ‐nucleoside‐diphosphate‐kinase inhibits ATP ‐induced reactive‐oxygen‐species via P 2 X 7 receptor/ NADPH ‐oxidase signalling and contributes to persistence
Author(s) -
Choi Chul Hee,
Spooner Ralee,
DeGuzman Jefferson,
Koutouzis Theofilos,
Ojcius David M.,
Yilmaz Özlem
Publication year - 2013
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/cmi.12089
Subject(s) - biology , nadph oxidase , porphyromonas gingivalis , reactive oxygen species , oxidase test , receptor , kinase , enzyme , biochemistry , genetics , bacteria
Summary Ligation of P 2 X 7 receptors with a ‘danger signal’, extracellular ATP ( eATP ), has recently been shown to result in production of intracellular reactive‐oxygen‐species ( ROS ) in macrophages. We show that primary gingival epithelial cells ( GECs ) produce sustained, robust cellular ROS upon stimulation by eATP . The induction of ROS was mediated by P 2 X 7 receptor signalling coupled with NADPH ‐oxidase activation, as determined by pharmacological inhibition and RNA interference. Furthermore, P orphyromonas gingivalis , an oral opportunistic pathogen, upregulated the antioxidant glutathione response, modulated eATP ‐induced cytosolic and mitochondrial ROS generated through P 2 X 7 / NADPH ‐oxidase interactome, and subsequently blocked oxidative stress in GECs via temporal secretion of a P . gingivalis effector, nucleoside‐diphosphate‐kinase ( N dk). An ndk ‐deficient P . gingivalis mutant lacked the ability to inhibit ROS production and persist intracellularly following eATP stimulation. Treatment with recombinant N dk significantly diminished eATP ‐evoked ROS production. P . gingivalis infection elicited a strong, time‐dependent increase in anti‐oxidativemitochondrial UCP 2 levels, whereas ndk ‐deficient mutant did not cause any change. The results reveal a novel signalling cascade that is tightly coupled with eATP signalling and ROS regulation. N dk by P . gingivalis counteracts these antimicrobial signalling activities by secreting N dk, thus contributing to successful persistence of the pathogen.

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