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标题：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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作者：Des R. Kashyap ; Dominik A. Kowalczyk ; Yue Shan 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2020
卷号：10
期号：1
页码：1-16
DOI：10.1038/s41598-020-58302-1
出版社：Springer Nature
摘要：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 (O 2 ) to hydrogen peroxide (H 2 O 2 ). In this study we identify the site of PGRP-induced generation of H 2 O 2 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 H 2 O 2 production and the highest resistance to PGRP-induced killing, and formate enhanced PGRP-induced killing and H 2 O 2 production in an FDH-dependent manner. Mutants in ubiquinone synthesis (but not menaquinone and demethylmenaquinone) and cytochrome bd -I (but not cytochromes bo 3 and bd -II) also had completely abolished PGRP-induced H 2 O 2 production and high resistance to PGRP-induced killing. Because electrons in the respiratory chain flow from dehydrogenases’ substrates through quinones and then cytochromes to O 2 , these results imply that the site of PGRP-induced incomplete reduction of O 2 to H 2 O 2 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.