8-OxoG-Dependent Regulation of Global Protein Responses Leads to Mutagenesis and Stress Survival in <i>Bacillus subtilis</i>
The guanine oxidized (GO) system of <i>Bacillus subtilis</i>, 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 <i>B. subtilis</i> cells, the genetic inactiva...
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-03-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/13/3/332 |
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| author | Lissett E. Martínez Gerardo Gómez Norma Ramírez Bernardo Franco Eduardo A. Robleto Mario Pedraza-Reyes |
| author_facet | Lissett E. Martínez Gerardo Gómez Norma Ramírez Bernardo Franco Eduardo A. Robleto Mario Pedraza-Reyes |
| author_sort | Lissett E. Martínez |
| collection | DOAJ |
| description | The guanine oxidized (GO) system of <i>Bacillus subtilis</i>, 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 <i>B. subtilis</i> cells, the genetic inactivation of GO system potentiated mutagenesis (HPM), and subsequent hyperresistance, contributes to the damaging effects of hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) (HPHR). The mechanism(s) that connect the accumulation of the mutagenic lesion 8-OxoG with the ability of <i>B. subtilis</i> 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 (<i>i</i>) cysteine catabolism, (<i>ii</i>) the synthesis of iron–sulfur clusters, (<i>iii</i>) the reorganization of cell wall architecture, (<i>iv</i>) the activation of AhpC/AhpF-independent organic peroxide resistance, and (<i>v</i>) increased resistance to transcription-acting antibiotics. Therefore, to contend with the cytotoxic and genotoxic effects derived from the accumulation of 8-OxoG, <i>B. subtilis</i> activates the synthesis of proteins belonging to transcriptional regulons that respond to a wide, diverse range of cell stressors. |
| first_indexed | 2024-04-24T18:36:40Z |
| format | Article |
| id | doaj.art-63c7cc55689d4e88a49b6a7fdeaf1c40 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-04-24T18:36:40Z |
| publishDate | 2024-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-63c7cc55689d4e88a49b6a7fdeaf1c402024-03-27T13:18:36ZengMDPI AGAntioxidants2076-39212024-03-0113333210.3390/antiox130303328-OxoG-Dependent Regulation of Global Protein Responses Leads to Mutagenesis and Stress Survival in <i>Bacillus subtilis</i>Lissett E. Martínez0Gerardo Gómez1Norma Ramírez2Bernardo Franco3Eduardo A. Robleto4Mario Pedraza-Reyes5Department of Biology, Division of Natural and Exact Sciences, University of Guanajuato, Guanajuato 36050, MexicoDepartment of Biology, Division of Natural and Exact Sciences, University of Guanajuato, Guanajuato 36050, MexicoDepartment of Biology, Division of Natural and Exact Sciences, University of Guanajuato, Guanajuato 36050, MexicoDepartment of Biology, Division of Natural and Exact Sciences, University of Guanajuato, Guanajuato 36050, MexicoSchool of Life Sciences, University of Nevada, Las Vegas, NV 89557, USADepartment of Biology, Division of Natural and Exact Sciences, University of Guanajuato, Guanajuato 36050, MexicoThe guanine oxidized (GO) system of <i>Bacillus subtilis</i>, 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 <i>B. subtilis</i> cells, the genetic inactivation of GO system potentiated mutagenesis (HPM), and subsequent hyperresistance, contributes to the damaging effects of hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) (HPHR). The mechanism(s) that connect the accumulation of the mutagenic lesion 8-OxoG with the ability of <i>B. subtilis</i> 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 (<i>i</i>) cysteine catabolism, (<i>ii</i>) the synthesis of iron–sulfur clusters, (<i>iii</i>) the reorganization of cell wall architecture, (<i>iv</i>) the activation of AhpC/AhpF-independent organic peroxide resistance, and (<i>v</i>) increased resistance to transcription-acting antibiotics. Therefore, to contend with the cytotoxic and genotoxic effects derived from the accumulation of 8-OxoG, <i>B. subtilis</i> activates the synthesis of proteins belonging to transcriptional regulons that respond to a wide, diverse range of cell stressors.https://www.mdpi.com/2076-3921/13/3/332<i>Bacillus subtilis</i>8-oxoGGO systemmutagenesisoxidative stress |
| spellingShingle | Lissett E. Martínez Gerardo Gómez Norma Ramírez Bernardo Franco Eduardo A. Robleto Mario Pedraza-Reyes 8-OxoG-Dependent Regulation of Global Protein Responses Leads to Mutagenesis and Stress Survival in <i>Bacillus subtilis</i> Antioxidants <i>Bacillus subtilis</i> 8-oxoG GO system mutagenesis oxidative stress |
| title | 8-OxoG-Dependent Regulation of Global Protein Responses Leads to Mutagenesis and Stress Survival in <i>Bacillus subtilis</i> |
| title_full | 8-OxoG-Dependent Regulation of Global Protein Responses Leads to Mutagenesis and Stress Survival in <i>Bacillus subtilis</i> |
| title_fullStr | 8-OxoG-Dependent Regulation of Global Protein Responses Leads to Mutagenesis and Stress Survival in <i>Bacillus subtilis</i> |
| title_full_unstemmed | 8-OxoG-Dependent Regulation of Global Protein Responses Leads to Mutagenesis and Stress Survival in <i>Bacillus subtilis</i> |
| title_short | 8-OxoG-Dependent Regulation of Global Protein Responses Leads to Mutagenesis and Stress Survival in <i>Bacillus subtilis</i> |
| title_sort | 8 oxog dependent regulation of global protein responses leads to mutagenesis and stress survival in i bacillus subtilis i |
| topic | <i>Bacillus subtilis</i> 8-oxoG GO system mutagenesis oxidative stress |
| url | https://www.mdpi.com/2076-3921/13/3/332 |
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