Elucidating the Mechanism of Temporal Adaptation to Hydrogen Peroxide‐Induced Oxidative Stress in Corynebacterium glutamicum

ABSTRACT Corynebacterium glutamicum serves as a pivotal industrial chassis for biomanufacturing and an ideal model for studying the phylogenetically related pathogen Mycobacterium tuberculosis. Oxidative stress poses a critical challenge to microorganisms during aerobic industrial processes and immu...

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Main Authors: Chang Yu, Wenjing Hu, Xiaoyu Li, Yu Lei, Dandan Gao, Meng Wang, Ping Zheng, Yan Zhu, Jibin Sun
Format: Article
Language:English
Published: Wiley 2025-06-01
Series:Microbial Biotechnology
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Online Access:https://doi.org/10.1111/1751-7915.70170
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author Chang Yu
Wenjing Hu
Xiaoyu Li
Yu Lei
Dandan Gao
Meng Wang
Ping Zheng
Yan Zhu
Jibin Sun
author_facet Chang Yu
Wenjing Hu
Xiaoyu Li
Yu Lei
Dandan Gao
Meng Wang
Ping Zheng
Yan Zhu
Jibin Sun
author_sort Chang Yu
collection DOAJ
description ABSTRACT Corynebacterium glutamicum serves as a pivotal industrial chassis for biomanufacturing and an ideal model for studying the phylogenetically related pathogen Mycobacterium tuberculosis. Oxidative stress poses a critical challenge to microorganisms during aerobic industrial processes and immune cell‐mediated antibacterial killing by perturbing cellular redox homeostasis, affecting central metabolism, and damaging the integrity of biomacromolecules. However, the intricate mechanisms underlying the dynamic defence of C. glutamicum, despite previous transcriptomic studies on acute and adaptive responses to oxidative stresses, remain largely unclear, hindering strain engineering for industrial applications and the development of effective antimicrobial treatments. In this study, the susceptibility of C. glutamicum to hydrogen peroxide (H2O2) was evaluated, and the inhibitory dynamics of H2O2 were characterised through viable cell counting. RNA sequencing (RNA‐seq) was employed to analyse gene expression changes after exposure to 720 mM H2O2. The treatment induced differential expression of 966 and 787 genes at 2 and 6 h, respectively, reflecting perturbations across a broad array of pathways, including (i) enhanced H2O2 and peroxide scavenging, mycothiol biosynthesis, and iron chelation; (ii) repressed central metabolism and enhanced anaplerosis; (iii) elevated sulphur assimilation; (iv) altered amino acid biosynthesis; and (v) altered transcriptional regulation in response to oxidative stress. Further validation by overexpression of ahpD, cysN, and exogenous supplementation with l‐methionine and l‐cysteine significantly enhanced bacterial tolerance to H2O2. Overall, this study provides the most comprehensive analysis to date of temporal cellular adaptation to H2O2 stress in C. glutamicum, establishing a foundation for future applications in both biomanufacturing and antimicrobial research.
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spelling doaj-art-6c3c61a2c84943eaa75fbfb50210995a2025-08-20T02:22:09ZengWileyMicrobial Biotechnology1751-79152025-06-01186n/an/a10.1111/1751-7915.70170Elucidating the Mechanism of Temporal Adaptation to Hydrogen Peroxide‐Induced Oxidative Stress in Corynebacterium glutamicumChang Yu0Wenjing Hu1Xiaoyu Li2Yu Lei3Dandan Gao4Meng Wang5Ping Zheng6Yan Zhu7Jibin Sun8Tianjin Institute of Industrial Biotechnology Chinese Academy of Sciences Tianjin ChinaTianjin Institute of Industrial Biotechnology Chinese Academy of Sciences Tianjin ChinaTianjin Institute of Industrial Biotechnology Chinese Academy of Sciences Tianjin ChinaTianjin Institute of Industrial Biotechnology Chinese Academy of Sciences Tianjin ChinaTianjin Institute of Industrial Biotechnology Chinese Academy of Sciences Tianjin ChinaTianjin Institute of Industrial Biotechnology Chinese Academy of Sciences Tianjin ChinaTianjin Institute of Industrial Biotechnology Chinese Academy of Sciences Tianjin ChinaTianjin Institute of Industrial Biotechnology Chinese Academy of Sciences Tianjin ChinaTianjin Institute of Industrial Biotechnology Chinese Academy of Sciences Tianjin ChinaABSTRACT Corynebacterium glutamicum serves as a pivotal industrial chassis for biomanufacturing and an ideal model for studying the phylogenetically related pathogen Mycobacterium tuberculosis. Oxidative stress poses a critical challenge to microorganisms during aerobic industrial processes and immune cell‐mediated antibacterial killing by perturbing cellular redox homeostasis, affecting central metabolism, and damaging the integrity of biomacromolecules. However, the intricate mechanisms underlying the dynamic defence of C. glutamicum, despite previous transcriptomic studies on acute and adaptive responses to oxidative stresses, remain largely unclear, hindering strain engineering for industrial applications and the development of effective antimicrobial treatments. In this study, the susceptibility of C. glutamicum to hydrogen peroxide (H2O2) was evaluated, and the inhibitory dynamics of H2O2 were characterised through viable cell counting. RNA sequencing (RNA‐seq) was employed to analyse gene expression changes after exposure to 720 mM H2O2. The treatment induced differential expression of 966 and 787 genes at 2 and 6 h, respectively, reflecting perturbations across a broad array of pathways, including (i) enhanced H2O2 and peroxide scavenging, mycothiol biosynthesis, and iron chelation; (ii) repressed central metabolism and enhanced anaplerosis; (iii) elevated sulphur assimilation; (iv) altered amino acid biosynthesis; and (v) altered transcriptional regulation in response to oxidative stress. Further validation by overexpression of ahpD, cysN, and exogenous supplementation with l‐methionine and l‐cysteine significantly enhanced bacterial tolerance to H2O2. Overall, this study provides the most comprehensive analysis to date of temporal cellular adaptation to H2O2 stress in C. glutamicum, establishing a foundation for future applications in both biomanufacturing and antimicrobial research.https://doi.org/10.1111/1751-7915.70170Corynebacterium glutamicumhydrogen peroxideindustrial stressredox homeostasistranscriptomic analysis
spellingShingle Chang Yu
Wenjing Hu
Xiaoyu Li
Yu Lei
Dandan Gao
Meng Wang
Ping Zheng
Yan Zhu
Jibin Sun
Elucidating the Mechanism of Temporal Adaptation to Hydrogen Peroxide‐Induced Oxidative Stress in Corynebacterium glutamicum
Microbial Biotechnology
Corynebacterium glutamicum
hydrogen peroxide
industrial stress
redox homeostasis
transcriptomic analysis
title Elucidating the Mechanism of Temporal Adaptation to Hydrogen Peroxide‐Induced Oxidative Stress in Corynebacterium glutamicum
title_full Elucidating the Mechanism of Temporal Adaptation to Hydrogen Peroxide‐Induced Oxidative Stress in Corynebacterium glutamicum
title_fullStr Elucidating the Mechanism of Temporal Adaptation to Hydrogen Peroxide‐Induced Oxidative Stress in Corynebacterium glutamicum
title_full_unstemmed Elucidating the Mechanism of Temporal Adaptation to Hydrogen Peroxide‐Induced Oxidative Stress in Corynebacterium glutamicum
title_short Elucidating the Mechanism of Temporal Adaptation to Hydrogen Peroxide‐Induced Oxidative Stress in Corynebacterium glutamicum
title_sort elucidating the mechanism of temporal adaptation to hydrogen peroxide induced oxidative stress in corynebacterium glutamicum
topic Corynebacterium glutamicum
hydrogen peroxide
industrial stress
redox homeostasis
transcriptomic analysis
url https://doi.org/10.1111/1751-7915.70170
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