Modeling nucleotide excision repair and its impact on UV-induced mutagenesis during SOS-response in bacterial cells

Bugay, A. N.; Krasavin, E. A.; Parkhomenko, A. Yu.; Vasilyeva, M. A.

doi:10.1016/j.jtbi.2014.08.041

Cited by 10 publications

(4 citation statements)

References 65 publications

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“…This dose-response relationship of the SOS response has been previously observed for pulses of UV damage (6, 9), but is not well described for continuous antibiotics exposure. Counting of LexA levels during CIP stress agreed qualitatively with previously reported pulsed UV exposure stress (6,(51)(52)(53). Surprisingly, even in unstressed cells, we found about 4 % of LexA in the cleaved fragment population, suggesting a low level of LexA fragmentation under normal growth conditions with a small, but detectable LexA turnover.…”

Section: Discussionsupporting

confidence: 90%

Direct visualization of four diffusive LexA states controlling SOS response strength during antibiotic treatment

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Tisma

Hartmann

et al. 2020

Preprint

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In bacteria, the key mechanism governing mutation, adaptation and survival upon DNA damage is the SOS response. Through autoproteolytic digestion triggered by single-stranded DNA caused by most antibiotics, the transcriptional repressor LexA controls over 50 SOS genes including DNA repair pathways and drivers of mutagenesis. Efforts to inhibit this response and thereby combat antibiotic resistance rely on a broad understanding of its behavior in vivo, which is still limited. Here, we develop a single-molecule localization microscopy assay to directly visualize LexA mobility in Escherichia coli and monitor the SOS response on the level of transcription factor activity. We identify four diffusive populations and monitor their temporal evolution upon ciprofloxacin-induced continuous DNA damage. With LexA mutants, we assign target bound, non-specifically DNA bound, freely diffusing and cleaved repressors. We develop a strategy to count LexA in fixed cells at different time points after antibiotic stress and combine the time-evolution of LexA sub-populations and the repressor's overall abundance. Through fitting a detailed kinetic model we obtain in vivo synthesis, cleavage and binding rates and determined that the regulatory feedback system reaches a new equilibrium in ~100 min. LexA concentrations showed non-constant heterogeneity during SOS response and designate LexA expression, and thereby regulation of downstream SOS proteins, as drivers of evolutionary adaptation. Even under low antibiotic stress, we observed a strong SOS response on the LexA level, suggestion that small amounts of antibiotics can trigger adaptation in E. coli.

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Section: Discussionsupporting

confidence: 90%

Direct visualization of four diffusive LexA states controlling SOS response strength during antibiotic treatment

Schaerfen

Tisma

Hartmann

et al. 2020

Preprint

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“…The ARTP mutagenesis can cause greater DNA damage with higher diversity than UV irradiation or chemical mutagens, because of the reactive chemical species produced by the helium-based ARTP system (Ottenheim et al 2018). DNA structure can be disrupted by these active chemicals, thereby inducing the microbial SOS repair system, which has a high error tolerance rate (Bugay et al 2015; Zhang et al 2015). Therefore, a variety of mismatches will be generated in the repair process, resulting in a large number of mutants.…”

Section: Discussionmentioning

confidence: 99%

Enhancement of ascomycin production via a combination of atmospheric and room temperature plasma mutagenesis in Streptomyces hygroscopicus and medium optimization

Shen

et al. 2019

AMB Expr

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Ascomycin, a key intermediate for chemical synthesis of immunosuppressive drug pimecrolimus, is produced by Streptomyces hygroscopicus var. ascomyceticus . In order to improve the strain production, the original S. hygroscopicus ATCC 14891 strain was treated here with atmospheric and room temperature plasma to obtain a stable high-producing S. hygroscopicus SFK-36 strain which produced 495.3 mg/L ascomycin, a 32.5% increase in ascomycin compared to the ATCC 14891. Then, fermentation medium was optimized using response surface methodology to further enhance ascomycin production. In the optimized medium containing 81.0 g/L soluble starch, 57.4 g/L peanut meal, and 15.8 g/L soybean oil, the ascomycin yield reached 1466.3 mg/L in flask culture. Furthermore, the fermentation process was carried out in a 5 L fermenter, and the ascomycin yield reached 1476.9 mg/L, which is the highest ascomycin yield reported so far. Therefore, traditional mutagenesis breeding combined with medium optimization is an effective approach for the enhancement of ascomycin production. Electronic supplementary material The online version of this article (10.1186/s13568-019-0749-x) contains supplementary material, which is available to authorized users.

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“…Meanwhile, semiconductor materials allowing for a wide-range of visiblelight harvesting should also be considered for biohybrid construction, which can on one hand prevent the detrimental photodamage of UV light on living organisms and on the other hand lead to more efficient usage of sun light. 123 In addition, current researches still mainly focus on the application of traditional metal-based semiconductors. Metal-free materials 55,74,93 that are more biocompatible and environmentally friendly are urgent to be developed for the construction of biohybrids.…”

Section: Discussionmentioning

confidence: 99%

“…The bandgap of desirable semiconductors should be regulated, so that the potentials of CB can be matched to those of electron transfer proteins or redox couples, , ensuring the redox reaction proceeding in the microorganisms. Meanwhile, semiconductor materials allowing for a wide-range of visible-light harvesting should also be considered for biohybrid construction, which can on one hand prevent the detrimental photodamage of UV light on living organisms and on the other hand lead to more efficient usage of sun light . In addition, current researches still mainly focus on the application of traditional metal-based semiconductors.…”

Section: Discussionmentioning

confidence: 99%

Photodriven Chemical Synthesis by Whole-Cell-Based Biohybrid Systems: From System Construction to Mechanism Study

Shen

Liu

Qiao

2023

ACS Appl. Mater. Interfaces

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By simulating natural photosynthesis, the desirable high-value chemical products and clean fuels can be sustainably generated with solar energy. Whole-cell-based photosensitized biohybrid system, which innovatively couples the excellent light-harvesting capacity of semiconductor materials with the efficient catalytic ability of intracellular biocatalysts, is an appealing interdisciplinary creature to realize photodriven chemical synthesis. In this review, we summarize the constructed whole-cell-based biohybrid systems in different application fields, including carbon dioxide fixation, nitrogen fixation, hydrogen production, and other chemical synthesis. Moreover, we elaborate the charge transfer mechanism studies of representative biohybrids, which can help to deepen the current understanding of the synergistic process between photosensitizers and microorganisms, and provide schemes for building novel biohybrids with less electron transfer resistance, advanced productive efficiency, and functional diversity. Further exploration in this field has the prospect of making a breakthrough on the biotic–abiotic interface that will provide opportunities for multidisciplinary research.

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Modeling nucleotide excision repair and its impact on UV-induced mutagenesis during SOS-response in bacterial cells

Cited by 10 publications

References 65 publications

Direct visualization of four diffusive LexA states controlling SOS response strength during antibiotic treatment

Direct visualization of four diffusive LexA states controlling SOS response strength during antibiotic treatment

Enhancement of ascomycin production via a combination of atmospheric and room temperature plasma mutagenesis in Streptomyces hygroscopicus and medium optimization

Photodriven Chemical Synthesis by Whole-Cell-Based Biohybrid Systems: From System Construction to Mechanism Study

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