No evidence of a role for mitochondrial complex I in Helicobacter pylori pathogenesis.
BACKGROUND
Complex I is the first enzyme complex in the mitochondrial respiratory chain, responsible for generating a large fraction of energy during oxidative phosphorylation. Recently, it has been identified that complex I deficiency can result in increased inflammation due to the generation of reactive oxygen species by innate immune cells. As a reduction in complex I activity has been demonstrated in human stomachs with atrophic gastritis, we investigated whether complex I deficiency could influence Helicobacter pylori pathogenesis.


METHODS
Ndufs6gt/gtmice have a partial complex I deficiency. Complex I activity was quantified in the stomachs and immune cells of Ndufs6gt/gtmice by spectrophotometric assays. Ndufs6gt/gtmice were infected with H. pylori and bacterial colonization assessed by colony-forming assay, gastritis assessed histologically, and H. pylori -specific humoral response quantified by ELISA.


RESULTS
The immune cells and stomachs of Ndufs6gt/gtmice were found to have significantly decreased complex I activity, validating the model for assessing the effects of complex I deficiency in H. pylori infection. However, there was no observable effect of complex I deficiency on either H. pylori colonization, the resulting gastritis, or the humoral response.


CONCLUSIONS
Although complex I activity is described to suppress innate immune responses and is decreased during atrophic gastritis in humans, our data suggest it does not affect H. pylori pathogenesis.
Murdoch Childrens Research Institute, The Royal Children's Hospital, Parkville, VIC 3052, Australia.|Centre for Animal Biotechnology, School of Veterinary and Agricultural Science, University of Melbourne, Parkville, VIC 3010, Australia.
Garrett Z
http://orcid.org/0000-0003-1742-6203
GZ
Ng
Murdoch Childrens Research Institute, The Royal Children's Hospital, Parkville, VIC 3052, Australia.
Bi-Xia
BX
Ke
Murdoch Childrens Research Institute, The Royal Children's Hospital, Parkville, VIC 3052, Australia.
Adrienne
A
Laskowski
Murdoch Childrens Research Institute, The Royal Children's Hospital, Parkville, VIC 3052, Australia.|Victorian Clinical Genetics Services, The Royal Children's Hospital, Parkville, VIC 3052, Australia.|Department of Paediatrics, University of Melbourne, Parkville, VIC 3010, Australia.
David R
DR
Thorburn
Murdoch Childrens Research Institute, The Royal Children's Hospital, Parkville, VIC 3052, Australia.|Centre for Animal Biotechnology, School of Veterinary and Agricultural Science, University of Melbourne, Parkville, VIC 3010, Australia.|Department of Paediatrics, University of Melbourne, Parkville, VIC 3010, Australia.
Philip
P
Sutton
D000818:Animals; D058491:Bacterial Load; D004195:Disease Models, Animal; D042967:Electron Transport Complex I / Q000172:deficiency / Q000378:metabolism*; D005260:Female; D005756:Gastritis / Q000473:pathology / Q000503:physiopathology*; D016481:Helicobacter Infections / Q000473:pathology / Q000503:physiopathology*; D016480:Helicobacter pylori / Q000472:pathogenicity*; D006651:Histocytochemistry; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008928:Mitochondria / Q000201:enzymology*
D042967:Electron Transport Complex I

Helicobacter pylori
; complex I; gastritis; mitochondria