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Glutathione Synthesis Regulated by CtrA Protects Ehrlichia chaffeensis From Host Cell Oxidative Stress
Ehrlichia chaffeensis, a small Gram-negative obligatory intracellular bacterium, infects human monocytes or macrophages, and causes human monocytic ehrlichiosis, one of the most prevalent, life-threatening emerging zoonoses. Reactive oxygen species are produced by the host immune cells in response t...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9005958/ https://www.ncbi.nlm.nih.gov/pubmed/35432225 http://dx.doi.org/10.3389/fmicb.2022.846488 |
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author | Yan, Jiaqi Liang, Qi’an Chai, Zhouyi Duan, Nan Li, Xiaoxiao Liu, Yajing Yang, Nan Li, Meifang Jin, Yongxin Bai, Fang Wu, Weihui Cheng, Zhihui |
author_facet | Yan, Jiaqi Liang, Qi’an Chai, Zhouyi Duan, Nan Li, Xiaoxiao Liu, Yajing Yang, Nan Li, Meifang Jin, Yongxin Bai, Fang Wu, Weihui Cheng, Zhihui |
author_sort | Yan, Jiaqi |
collection | PubMed |
description | Ehrlichia chaffeensis, a small Gram-negative obligatory intracellular bacterium, infects human monocytes or macrophages, and causes human monocytic ehrlichiosis, one of the most prevalent, life-threatening emerging zoonoses. Reactive oxygen species are produced by the host immune cells in response to bacterial infections. The mechanisms exploited by E. chaffeensis to resist oxidative stress have not been comprehensively demonstrated. Here, we found that E. chaffeensis encodes two functional enzymes, GshA and GshB, to synthesize glutathione that confers E. chaffeensis the oxidative stress resistance, and that the expression of gshA and gshB is upregulated by CtrA, a global transcriptional regulator, upon oxidative stress. We found that in E. chaffeensis, the expression of gshA and gshB was upregulated upon oxidative stress using quantitative RT-PCR. Ehrlichia chaffeensis GshA or GshB restored the ability of Pseudomonas aeruginosa GshA or GshB mutant to cope with oxidative stress, respectively. Recombinant E. chaffeensis CtrA directly bound to the promoters of gshA and gshB, determined with electrophoretic mobility shift assay, and activated the expression of gshA and gshB determined with reporter assay. Peptide nucleic acid transfection of E. chaffeensis, which reduced the CtrA protein level, inhibited the oxidative stress-induced upregulation of gshA and gshB. Our findings provide insights into the function and regulation of the two enzymes critical for E. chaffeensis resistance to oxidative stress and may deepen our understanding of E. chaffeensis pathogenesis and adaptation in hosts. |
format | Online Article Text |
id | pubmed-9005958 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-90059582022-04-14 Glutathione Synthesis Regulated by CtrA Protects Ehrlichia chaffeensis From Host Cell Oxidative Stress Yan, Jiaqi Liang, Qi’an Chai, Zhouyi Duan, Nan Li, Xiaoxiao Liu, Yajing Yang, Nan Li, Meifang Jin, Yongxin Bai, Fang Wu, Weihui Cheng, Zhihui Front Microbiol Microbiology Ehrlichia chaffeensis, a small Gram-negative obligatory intracellular bacterium, infects human monocytes or macrophages, and causes human monocytic ehrlichiosis, one of the most prevalent, life-threatening emerging zoonoses. Reactive oxygen species are produced by the host immune cells in response to bacterial infections. The mechanisms exploited by E. chaffeensis to resist oxidative stress have not been comprehensively demonstrated. Here, we found that E. chaffeensis encodes two functional enzymes, GshA and GshB, to synthesize glutathione that confers E. chaffeensis the oxidative stress resistance, and that the expression of gshA and gshB is upregulated by CtrA, a global transcriptional regulator, upon oxidative stress. We found that in E. chaffeensis, the expression of gshA and gshB was upregulated upon oxidative stress using quantitative RT-PCR. Ehrlichia chaffeensis GshA or GshB restored the ability of Pseudomonas aeruginosa GshA or GshB mutant to cope with oxidative stress, respectively. Recombinant E. chaffeensis CtrA directly bound to the promoters of gshA and gshB, determined with electrophoretic mobility shift assay, and activated the expression of gshA and gshB determined with reporter assay. Peptide nucleic acid transfection of E. chaffeensis, which reduced the CtrA protein level, inhibited the oxidative stress-induced upregulation of gshA and gshB. Our findings provide insights into the function and regulation of the two enzymes critical for E. chaffeensis resistance to oxidative stress and may deepen our understanding of E. chaffeensis pathogenesis and adaptation in hosts. Frontiers Media S.A. 2022-03-30 /pmc/articles/PMC9005958/ /pubmed/35432225 http://dx.doi.org/10.3389/fmicb.2022.846488 Text en Copyright © 2022 Yan, Liang, Chai, Duan, Li, Liu, Yang, Li, Jin, Bai, Wu and Cheng. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Microbiology Yan, Jiaqi Liang, Qi’an Chai, Zhouyi Duan, Nan Li, Xiaoxiao Liu, Yajing Yang, Nan Li, Meifang Jin, Yongxin Bai, Fang Wu, Weihui Cheng, Zhihui Glutathione Synthesis Regulated by CtrA Protects Ehrlichia chaffeensis From Host Cell Oxidative Stress |
title | Glutathione Synthesis Regulated by CtrA Protects Ehrlichia chaffeensis From Host Cell Oxidative Stress |
title_full | Glutathione Synthesis Regulated by CtrA Protects Ehrlichia chaffeensis From Host Cell Oxidative Stress |
title_fullStr | Glutathione Synthesis Regulated by CtrA Protects Ehrlichia chaffeensis From Host Cell Oxidative Stress |
title_full_unstemmed | Glutathione Synthesis Regulated by CtrA Protects Ehrlichia chaffeensis From Host Cell Oxidative Stress |
title_short | Glutathione Synthesis Regulated by CtrA Protects Ehrlichia chaffeensis From Host Cell Oxidative Stress |
title_sort | glutathione synthesis regulated by ctra protects ehrlichia chaffeensis from host cell oxidative stress |
topic | Microbiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9005958/ https://www.ncbi.nlm.nih.gov/pubmed/35432225 http://dx.doi.org/10.3389/fmicb.2022.846488 |
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