{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Beebout CJ"],"funding":["U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences","Howard Hughes Medical Institute","NCRR NIH HHS","NIAID NIH HHS","U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases","NIMH NIH HHS","Division of Intramural Research, National Institute of Allergy and Infectious Diseases","NEI NIH HHS","NIDDK NIH HHS","NCI NIH HHS","NINDS NIH HHS","NIGMS NIH HHS","U.S. Department of Health & Human Services | National Institutes of Health","NIH HHS","U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases"],"pagination":["1348-1360"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9756876"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["7(9)"],"pubmed_abstract":["Urinary tract infections are among the most common human bacterial infections and place a significant burden on healthcare systems due to associated morbidity, cost and antibiotic use. Despite being a facultative anaerobe, uropathogenic Escherichia coli, the primary cause of urinary tract infections, requires aerobic respiration to establish infection in the bladder. Here, by combining bacterial genetics with cell culture and murine models of infection, we demonstrate that the widely conserved respiratory quinol oxidase cytochrome bd is required for intracellular infection of urothelial cells. Through a series of genetic, biochemical and functional assays, we show that intracellular oxygen scavenging by cytochrome bd alters mitochondrial physiology by reducing the efficiency of mitochondrial respiration, stabilizing the hypoxia-inducible transcription factor HIF-1 and promoting a shift towards aerobic glycolysis. This bacterially induced rewiring of host metabolism antagonizes apoptosis, thereby protecting intracellular bacteria from urothelial cell exfoliation and preserving their replicative niche. These results reveal the metabolic basis for intracellular bacterial pathogenesis during urinary tract infection and identify subversion of mitochondrial metabolism as a bacterial strategy to facilitate persistence within the urinary tract."],"journal":["Nature microbiology"],"pubmed_title":["Uropathogenic Escherichia coli subverts mitochondrial metabolism to enable intracellular bacterial pathogenesis in urinary tract infection."],"pmcid":["PMC9756876"],"funding_grant_id":["R01 AI127793","RF1 MH123971","P20DK123967","R01DK105550","T32 GM007347","Gilliam Award","P30 EY008126","T32 GM007569","R01 DK105550","P30 DK020593","F99 NS125829","F32CA250258","UL1 RR024975","G20 RR030956","R35GM128915","T32GM007569","P20 DK123967","T32GM007347","R01AI107052","R01AI101171","F32 CA250258","F99NS125829","F30 AI150077","S10 RR031634","T32 AI112541","P30 CA068485","S10 OD023680","F30 CA247202","R01 AI107052","R35 GM128915","R01AI127793","F30AI150077","R01 AI101171","T32AI112541"],"pubmed_authors":["Beebout CJ","Brannon JR","Gama V","Blee AM","Robertson GL","Chazin WJ","Reinfeld BI","Rathmell JC","Hadjifrangiskou M","Rathmell WK","Morales GH"],"additional_accession":[]},"is_claimable":false,"name":"Uropathogenic Escherichia coli subverts mitochondrial metabolism to enable intracellular bacterial pathogenesis in urinary tract infection.","description":"Urinary tract infections are among the most common human bacterial infections and place a significant burden on healthcare systems due to associated morbidity, cost and antibiotic use. Despite being a facultative anaerobe, uropathogenic Escherichia coli, the primary cause of urinary tract infections, requires aerobic respiration to establish infection in the bladder. Here, by combining bacterial genetics with cell culture and murine models of infection, we demonstrate that the widely conserved respiratory quinol oxidase cytochrome bd is required for intracellular infection of urothelial cells. Through a series of genetic, biochemical and functional assays, we show that intracellular oxygen scavenging by cytochrome bd alters mitochondrial physiology by reducing the efficiency of mitochondrial respiration, stabilizing the hypoxia-inducible transcription factor HIF-1 and promoting a shift towards aerobic glycolysis. This bacterially induced rewiring of host metabolism antagonizes apoptosis, thereby protecting intracellular bacteria from urothelial cell exfoliation and preserving their replicative niche. These results reveal the metabolic basis for intracellular bacterial pathogenesis during urinary tract infection and identify subversion of mitochondrial metabolism as a bacterial strategy to facilitate persistence within the urinary tract.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Sep","modification":"2026-05-31T11:03:11.074Z","creation":"2025-04-19T10:47:16.851Z"},"accession":"S-EPMC9756876","cross_references":{"pubmed":["35995841"],"doi":["10.1038/s41564-022-01205-w"]}}