8-OxoG-Dependent Regulation of Global Protein Responses Leads to Mutagenesis and Stress Survival in Bacillus subtilis

• Published in: Antioxidants 2024-03, Vol.13 (3), p.332
• Main Authors: Martínez, Lissett E, Gómez, Gerardo, Ramírez, Norma, Franco, Bernardo, Robleto, Eduardo A, Pedraza-Reyes, Mario
• Format: Article
• Language: English
• Subjects: 8-oxoG; Antibiotics; Bacillus subtilis; Bacteria; Cell walls; Cytotoxicity; Genotoxicity; GO system; Hydrogen peroxide; Microorganisms; Mutagenesis; Mutation; Oxidative stress; Particle size; Peptides; Phenotypes; Pore size; Proteins; Proteomes
• ISSN: 2076-3921; 2076-3921
• DOI: 10.3390/antiox13030332

The guanine oxidized (GO) system of , composed of the YtkD (MutT), MutM and MutY proteins, counteracts the cytotoxic and genotoxic effects of the oxidized nucleobase 8-OxoG. Here, we report that in growing cells, the genetic inactivation of GO system potentiated mutagenesis (HPM), and subsequent hyperresistance, contributes to the damaging effects of hydrogen peroxide (H O ) (HPHR). The mechanism(s) that connect the accumulation of the mutagenic lesion 8-OxoG with the ability of to evolve and survive the noxious effects of oxidative stress were dissected. Genetic and biochemical evidence indicated that the synthesis of KatA was exacerbated, in a PerR-independent manner, and the transcriptional coupling repair factor, Mfd, contributed to HPHR and HPM of the ΔGO strain. Moreover, these phenotypes are associated with wider pleiotropic effects, as revealed by a global proteome analysis. The inactivation of the GO system results in the upregulated production of KatA, and it reprograms the synthesis of the proteins involved in distinct types of cellular stress; this has a direct impact on ( ) cysteine catabolism, ( ) the synthesis of iron-sulfur clusters, ( ) the reorganization of cell wall architecture, ( ) the activation of AhpC/AhpF-independent organic peroxide resistance, and ( ) increased resistance to transcription-acting antibiotics. Therefore, to contend with the cytotoxic and genotoxic effects derived from the accumulation of 8-OxoG, activates the synthesis of proteins belonging to transcriptional regulons that respond to a wide, diverse range of cell stressors.