Respiratory chain components are required for peptidoglycan recognition protein-induced thiol depletion and killing in Bacillus subtilis and Escherichia coli

Abstract Mammalian peptidoglycan recognition proteins (PGRPs or PGLYRPs) kill bacteria through induction of synergistic oxidative, thiol, and metal stress. Tn-seq screening of Bacillus subtilis transposon insertion library revealed that mutants in the shikimate pathway of chorismate synthesis had hi...

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Autores principales: Chun-Kai Yang, Des R. Kashyap, Dominik A. Kowalczyk, David Z. Rudner, Xindan Wang, Dipika Gupta, Roman Dziarski
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Publicado: Nature Portfolio 2021
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spelling oai:doaj.org-article:5242925f79604c4da0d4aa89b70fd3642021-12-02T15:08:21ZRespiratory chain components are required for peptidoglycan recognition protein-induced thiol depletion and killing in Bacillus subtilis and Escherichia coli10.1038/s41598-020-79811-z2045-2322https://doaj.org/article/5242925f79604c4da0d4aa89b70fd3642021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-79811-zhttps://doaj.org/toc/2045-2322Abstract Mammalian peptidoglycan recognition proteins (PGRPs or PGLYRPs) kill bacteria through induction of synergistic oxidative, thiol, and metal stress. Tn-seq screening of Bacillus subtilis transposon insertion library revealed that mutants in the shikimate pathway of chorismate synthesis had high survival following PGLYRP4 treatment. Deletion mutants for these genes had decreased amounts of menaquinone (MK), increased resistance to killing, and attenuated depletion of thiols following PGLYRP4 treatment. These effects were reversed by MK or reproduced by inhibiting MK synthesis. Deletion of cytochrome aa 3 -600 or NADH dehydrogenase (NDH) genes also increased B. subtilis resistance to PGLYRP4-induced killing and attenuated thiol depletion. PGLYRP4 treatment also inhibited B. subtilis respiration. Similarly in Escherichia coli, deletion of ubiquinone (UQ) synthesis, formate dehydrogenases (FDH), NDH-1, or cytochrome bd-I genes attenuated PGLYRP4-induced thiol depletion. PGLYRP4-induced low level of cytoplasmic membrane depolarization in B. subtilis and E. coli was likely not responsible for thiol depletion. Thus, our results show that the respiratory electron transport chain components, cytochrome aa 3 -600, MK, and NDH in B. subtilis, and cytochrome bd-I, UQ, FDH-O, and NDH-1 in E. coli, are required for both PGLYRP4-induced killing and thiol depletion and indicate conservation of the PGLYRP4-induced thiol depletion and killing mechanisms in Gram-positive and Gram-negative bacteria.Chun-Kai YangDes R. KashyapDominik A. KowalczykDavid Z. RudnerXindan WangDipika GuptaRoman DziarskiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-18 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Chun-Kai Yang
Des R. Kashyap
Dominik A. Kowalczyk
David Z. Rudner
Xindan Wang
Dipika Gupta
Roman Dziarski
Respiratory chain components are required for peptidoglycan recognition protein-induced thiol depletion and killing in Bacillus subtilis and Escherichia coli
description Abstract Mammalian peptidoglycan recognition proteins (PGRPs or PGLYRPs) kill bacteria through induction of synergistic oxidative, thiol, and metal stress. Tn-seq screening of Bacillus subtilis transposon insertion library revealed that mutants in the shikimate pathway of chorismate synthesis had high survival following PGLYRP4 treatment. Deletion mutants for these genes had decreased amounts of menaquinone (MK), increased resistance to killing, and attenuated depletion of thiols following PGLYRP4 treatment. These effects were reversed by MK or reproduced by inhibiting MK synthesis. Deletion of cytochrome aa 3 -600 or NADH dehydrogenase (NDH) genes also increased B. subtilis resistance to PGLYRP4-induced killing and attenuated thiol depletion. PGLYRP4 treatment also inhibited B. subtilis respiration. Similarly in Escherichia coli, deletion of ubiquinone (UQ) synthesis, formate dehydrogenases (FDH), NDH-1, or cytochrome bd-I genes attenuated PGLYRP4-induced thiol depletion. PGLYRP4-induced low level of cytoplasmic membrane depolarization in B. subtilis and E. coli was likely not responsible for thiol depletion. Thus, our results show that the respiratory electron transport chain components, cytochrome aa 3 -600, MK, and NDH in B. subtilis, and cytochrome bd-I, UQ, FDH-O, and NDH-1 in E. coli, are required for both PGLYRP4-induced killing and thiol depletion and indicate conservation of the PGLYRP4-induced thiol depletion and killing mechanisms in Gram-positive and Gram-negative bacteria.
format article
author Chun-Kai Yang
Des R. Kashyap
Dominik A. Kowalczyk
David Z. Rudner
Xindan Wang
Dipika Gupta
Roman Dziarski
author_facet Chun-Kai Yang
Des R. Kashyap
Dominik A. Kowalczyk
David Z. Rudner
Xindan Wang
Dipika Gupta
Roman Dziarski
author_sort Chun-Kai Yang
title Respiratory chain components are required for peptidoglycan recognition protein-induced thiol depletion and killing in Bacillus subtilis and Escherichia coli
title_short Respiratory chain components are required for peptidoglycan recognition protein-induced thiol depletion and killing in Bacillus subtilis and Escherichia coli
title_full Respiratory chain components are required for peptidoglycan recognition protein-induced thiol depletion and killing in Bacillus subtilis and Escherichia coli
title_fullStr Respiratory chain components are required for peptidoglycan recognition protein-induced thiol depletion and killing in Bacillus subtilis and Escherichia coli
title_full_unstemmed Respiratory chain components are required for peptidoglycan recognition protein-induced thiol depletion and killing in Bacillus subtilis and Escherichia coli
title_sort respiratory chain components are required for peptidoglycan recognition protein-induced thiol depletion and killing in bacillus subtilis and escherichia coli
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/5242925f79604c4da0d4aa89b70fd364
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AT dominikakowalczyk respiratorychaincomponentsarerequiredforpeptidoglycanrecognitionproteininducedthioldepletionandkillinginbacillussubtilisandescherichiacoli
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AT xindanwang respiratorychaincomponentsarerequiredforpeptidoglycanrecognitionproteininducedthioldepletionandkillinginbacillussubtilisandescherichiacoli
AT dipikagupta respiratorychaincomponentsarerequiredforpeptidoglycanrecognitionproteininducedthioldepletionandkillinginbacillussubtilisandescherichiacoli
AT romandziarski respiratorychaincomponentsarerequiredforpeptidoglycanrecognitionproteininducedthioldepletionandkillinginbacillussubtilisandescherichiacoli
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