Work

Characterizing Common Factors Affecting Replication Initiation During H2O2 Exposure and Genetic Mutation-Induced Oxidative Stress in Escherichia coli

Year: 2025

Type: article

Abstract: Oxidative stress is prevalent in organisms, and excessive oxidative damage can trigger cell death. Bacteria have evolved multiple pathways to cope with adverse stress, including the regulation of the cell cycle. Previous studies show that non-lethal exposure to H2O2 and mutations in antioxidant enzymes suppress replication initiation in Escherichia coli. The existence of common regulatory factors governing replication initiation across diverse causes-induced oxidative stress remains unclear. In this study, we utilized flow cytometry to determine the replication pattern of E. coli, and found that oxidative stress also participated in the inhibition of replication initiation by a defective iron regulation (fur-bfr-dps deletion). Adding a certain level of ATP promoted replication initiation in various antioxidant enzyme-deficient mutants and the ΔfurΔbfrΔdps mutant, suggesting that low ATP levels could be a common factor in the inhibition of replication initiation by different causes-induced oxidative stress. More potential common factors were screened using proteomics, followed by genetic validation with H2O2 stress. We found that oxidative stress might mediate the inhibition of replication initiation by interfering with the metabolism of glycine, glutamate, ornithine, and aspartate. Blocking CcmA-dependent cytochrome c biosynthesis, deleting the efflux pump proteins MdtABCD and TolC, or the arabinose transporter AraFHG eliminated the replication initiation inhibition by H2O2. In conclusion, this study uncovers a common multifactorial pathway of different causes-induced oxidative stress inhibiting replication initiation. Dormant and persistent bacteria exhibit an arrested or slow cell cycle, and non-lethal oxidative stress promotes their formation. Our findings contribute to exploring strategies to limit dormant and persistent bacterial formation by maintaining faster DNA replication initiation (cell cycle progression).

Source: International Journal of Molecular Sciences

DOI: 10.3390/ijms26072968

Authors: Jiaxin Qiao, Weiwei Zhu, Dongdong Du, Morigen Morigen

Institutions: Inner Mongolia University, Xiamen University, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics

Language: English

Topic: Bacterial Genetics and Biotechnology

Subfield: Genetics

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,499