RRC ID 59085
著者 Kashyap DR, Kowalczyk DA, Shan Y, Yang CK, Gupta D, Dziarski R.
タイトル Formate dehydrogenase, ubiquinone, and cytochrome bd-I are required for peptidoglycan recognition protein-induced oxidative stress and killing in Escherichia coli.
ジャーナル Sci Rep
Abstract Mammalian Peptidoglycan Recognition Proteins (PGRPs) kill bacteria through induction of synergistic oxidative, thiol, and metal stress. PGRPs induce oxidative stress in bacteria through a block in the respiratory chain, which results in decreased respiration and incomplete reduction of oxygen (O2) to hydrogen peroxide (H2O2). In this study we identify the site of PGRP-induced generation of H2O2 in Escherichia coli. Tn-seq screening of E. coli Tn10 insertion library revealed that mutants in formate dehydrogenase (FDH) genes had the highest survival following PGRP treatment. Mutants lacking functional FDH-O had abolished PGRP-induced H2O2 production and the highest resistance to PGRP-induced killing, and formate enhanced PGRP-induced killing and H2O2 production in an FDH-dependent manner. Mutants in ubiquinone synthesis (but not menaquinone and demethylmenaquinone) and cytochrome bd-I (but not cytochromes bo3 and bd-II) also had completely abolished PGRP-induced H2O2 production and high resistance to PGRP-induced killing. Because electrons in the respiratory chain flow from dehydrogenases' substrates through quinones and then cytochromes to O2, these results imply that the site of PGRP-induced incomplete reduction of O2 to H2O2 is downstream from dehydrogenases and ubiquinone at the level of cytochrome bd-I, which results in oxidative stress. These results reveal several essential steps in PGRP-induced bacterial killing.
巻・号 10(1)
ページ 1993
公開日 2020-2-6
DOI 10.1038/s41598-020-58302-1
PII 10.1038/s41598-020-58302-1
PMID 32029761
PMC PMC7005000
MeSH Animals Carrier Proteins / genetics Carrier Proteins / isolation & purification Carrier Proteins / metabolism* Cell Line Cytochrome d Group / biosynthesis Cytochromes b / biosynthesis Drosophila melanogaster Escherichia coli / physiology* Escherichia coli Proteins / genetics Escherichia coli Proteins / metabolism* Formate Dehydrogenases / genetics Formate Dehydrogenases / metabolism* Host Microbial Interactions* Humans Hydrogen Peroxide / metabolism Mutation Oxidation-Reduction Oxidative Stress / physiology Recombinant Proteins / genetics Recombinant Proteins / isolation & purification Recombinant Proteins / metabolism Ubiquinone / biosynthesis
IF 4.011
引用数 0
リソース情報
原核生物(大腸菌) Keio collection