A LexA-independent redox-based transcriptional regulation to DNA damage response system in mycobacteria
- 1State Key Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences
- 2Guangzhou Medical University
Abstract
Background The bacterial DNA damage response (DDR) system promotes survival under stressful conditions and facilitates the emergence of drug-resistant mutations. The DDR system in Mycobacterium tuberculosis is primarily governed by LexA-mediated transcriptional repression. Although some other regulators, such as PafBC and McdR have been reported, whether additional regulatory inputs contribute to DDR remains to be characterized. Results By performing a bacterial one-hybrid screen, we identified several transcriptional regulators, including Rv2282c, Rv1985c and Rv1990c, that activate DDR gene expression and inhibit cell growth. Promoter truncation analysis revealed that these regulators act through sequences distinct from the canonical LexA-binding motif. No specific interaction between these regulators and DDR gene promoters was detected by EMSAs, indicating an indirect regulatory mechanism. RNA-seq analysis revealed that approximately 25% genes were differentially expressed upon overexpression of each of these regulators. Among these, tpx, which is responsible for oxidative stress defense, was consistently repressed by all of the three DDR-activating regulators but not by control regulators. Complementation of Tpx alleviated ROS accumulation and restored cell growth in strains overexpressing these regulators, suggesting that the DDR activation is linked to redox imbalance caused by Tpx repression. Conclusions Our data demonstrate that Rv2282c, Rv1985c, and Rv1990c activate the DDR through perturbation of redox homeostasis, revealing a previously unrecognized, LexA-independent regulation pathway in mycobacteria.
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BibTeX
@article{li2026lexaindependent,
title = {{A LexA-independent redox-based transcriptional regulation to DNA damage response system in mycobacteria}},
author = {Sige Li and Zhiyong Wu and Wei Zhou and Chun Wang and Xindi Huang and Wenjing Yu and Yong Zhang and Shiyun Chen and Yangbo Hu},
journal = {BMC Microbiology},
year = {2026},
month = jul,
doi = {10.1186/s12866-026-05449-y},
url = {https://doi.org/10.1186/s12866-026-05449-y},
note = {CC BY},
}
RIS
TY - JOUR
TI - A LexA-independent redox-based transcriptional regulation to DNA damage response system in mycobacteria
AU - Sige Li
AU - Zhiyong Wu
AU - Wei Zhou
AU - Chun Wang
AU - Xindi Huang
AU - Wenjing Yu
AU - Yong Zhang
AU - Shiyun Chen
AU - Yangbo Hu
PY - 2026
DA - 2026/07/01
JO - BMC Microbiology
DO - 10.1186/s12866-026-05449-y
UR - https://doi.org/10.1186/s12866-026-05449-y
AB - Background The bacterial DNA damage response (DDR) system promotes survival under stressful conditions and facilitates the emergence of drug-resistant mutations. The DDR system in Mycobacterium tuberculosis is primarily governed by LexA-mediated transcriptional repression. Although some other regulators, such as PafBC and McdR have been reported, whether additional regulatory inputs contribute to DDR remains to be characterized. Results By performing a bacterial one-hybrid screen, we identified several transcriptional regulators, including Rv2282c, Rv1985c and Rv1990c, that activate DDR gene expression and inhibit cell growth. Promoter truncation analysis revealed that these regulators act through sequences distinct from the canonical LexA-binding motif. No specific interaction between these regulators and DDR gene promoters was detected by EMSAs, indicating an indirect regulatory mechanism. RNA-seq analysis revealed that approximately 25% genes were differentially expressed upon overexpression of each of these regulators. Among these, tpx, which is responsible for oxidative stress defense, was consistently repressed by all of the three DDR-activating regulators but not by control regulators. Complementation of Tpx alleviated ROS accumulation and restored cell growth in strains overexpressing these regulators, suggesting that the DDR activation is linked to redox imbalance caused by Tpx repression. Conclusions Our data demonstrate that Rv2282c, Rv1985c, and Rv1990c activate the DDR through perturbation of redox homeostasis, revealing a previously unrecognized, LexA-independent regulation pathway in mycobacteria.
SN - 1471-2180
ER -