RRC ID |
59085
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著者 |
Kashyap DR, Kowalczyk DA, Shan Y, Yang CK, Gupta D, Dziarski R.
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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.
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ジャーナル |
Sci Rep
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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.
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巻・号 |
10(1)
|
ページ |
1993
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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
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リソース情報 |
原核生物(大腸菌) |
Keio collection |