Increased Mutation Frequency in Redox-Impaired
            <i>Escherichia coli</i>
            Due to RelA- and RpoS-Mediated Repression of DNA Repair

Singh, Amarjeet; Karimpour-Fard, Anis; Gill, Ryan T.

doi:10.1128/aem.00583-10

Cited by 6 publications

(4 citation statements)

References 79 publications

(101 reference statements)

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“…The mutation frequency was measured by treating cell cultures with furfural and then plating with rifampin to measure the number of spontaneous mutants, compared to total viable cells ( Fig. 4B ) [54] , [55] . Surprisingly, no clones exhibited significantly altered DNA mutation frequency from control ( p >0.05 for all).…”

Section: Resultsmentioning

confidence: 99%

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Genome-Wide Mapping of Furfural Tolerance Genes in Escherichia coli

et al. 2014

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Advances in genomics have improved the ability to map complex genotype-to-phenotype relationships, like those required for engineering chemical tolerance. Here, we have applied the multiSCale Analysis of Library Enrichments (SCALEs; Lynch et al. (2007) Nat. Method.) approach to map, in parallel, the effect of increased dosage for >105 different fragments of the Escherichia coli genome onto furfural tolerance (furfural is a key toxin of lignocellulosic hydrolysate). Only 268 of >4,000 E. coli genes (∼6%) were enriched after growth selections in the presence of furfural. Several of the enriched genes were cloned and tested individually for their effect on furfural tolerance. Overexpression of thyA, lpcA, or groESL individually increased growth in the presence of furfural. Overexpression of lpcA, but not groESL or thyA, resulted in increased furfural reduction rate, a previously identified mechanism underlying furfural tolerance. We additionally show that plasmid-based expression of functional LpcA or GroESL is required to confer furfural tolerance. This study identifies new furfural tolerant genes, which can be applied in future strain design efforts focused on the production of fuels and chemicals from lignocellulosic hydrolysate.

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Section: Resultsmentioning

confidence: 99%

“…Mutation frequency was measured by proxy with frequency of rifampin resistance [54] , [55] . Cell cultures were grown overnight, harvested by centrifugation, diluted 10-fold into 25 ml of MOPS minimal medium, and incubated for 30 minutes to allow for growth to begin.…”

Section: Methodsmentioning

confidence: 99%

Genome-Wide Mapping of Furfural Tolerance Genes in Escherichia coli

et al. 2014

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“…In some cases, there would be an additional change in the redox ratio rendering this process irreversible, and hence leading to cell death 5. Following the initial revelation of the linkage between the increase in redox ratio and bacterial cidality, there has been limited corroboration of this former phenomenon,17,18 including the generation of reactive oxygen species. Possibly due to the diffusion/export of the cofactor to the growth media, in an experimental scale this change could be transitory and hence prove difficult to detect.…”

Section: Resultsmentioning

confidence: 99%

Genetic and chemical knockdown: a complementary strategy for evaluating an anti-infective target

Ramachandran

Rg²,

Yang³

et al. 2013

AABC

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The equity of a drug target is principally evaluated by its genetic vulnerability with tools ranging from antisense- and microRNA-driven knockdowns to induced expression of the target protein. In order to upgrade the process of antibacterial target identification and discern its most effective type of inhibition, an in silico toolbox that evaluates its genetic and chemical vulnerability leading either to stasis or cidal outcome was constructed and validated. By precise simulation and careful experimentation using enolpyruvyl shikimate-3-phosphate synthase and its specific inhibitor glyphosate, it was shown that genetic knockdown is distinct from chemical knockdown. It was also observed that depending on the particular mechanism of inhibition, viz competitive, uncompetitive, and noncompetitive, the antimicrobial potency of an inhibitor could be orders of magnitude different. Susceptibility of Escherichia coli to glyphosate and the lack of it in Mycobacterium tuberculosis could be predicted by the in silico platform. Finally, as predicted and simulated in the in silico platform, the translation of growth inhibition to a cidal effect was able to be demonstrated experimentally by altering the carbon source from sorbitol to glucose.

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“…Oxygen presence potentiates oxygen detoxification mechanisms and elevates catalases and hydroperoxidases (254), and mutational processes are also affected differentially by aspects of aerobic/anaerobic metabolism (299). Hence, a population changing from an anaerobic to an aerobic environment may be more stressed by the same transition than one coming from aerobiosis.…”

Section: Prior Stress Exposurementioning

confidence: 99%

Culture History and Population Heterogeneity as Determinants of Bacterial Adaptation: the Adaptomics of a Single Environmental Transition

Ryall

Eydallin

Ferenci

2012

Microbiol Mol Biol Rev

140

109

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SUMMARY Diversity in adaptive responses is common within species and populations, especially when the heterogeneity of the frequently large populations found in environments is considered. By focusing on events in a single clonal population undergoing a single transition, we discuss how environmental cues and changes in growth rate initiate a multiplicity of adaptive pathways. Adaptation is a comprehensive process, and stochastic, regulatory, epigenetic, and mutational changes can contribute to fitness and overlap in timing and frequency. We identify culture history as a major determinant of both regulatory adaptations and microevolutionary change. Population history before a transition determines heterogeneities due to errors in translation, stochastic differences in regulation, the presence of aged, damaged, cheating, or dormant cells, and variations in intracellular metabolite or regulator concentrations. It matters whether bacteria come from dense, slow-growing, stressed, or structured states. Genotypic adaptations are history dependent due to variations in mutation supply, contingency gene changes, phase variation, lateral gene transfer, and genome amplifications. Phenotypic adaptations underpin genotypic changes in situations such as stress-induced mutagenesis or prophage induction or in biofilms to give a continuum of adaptive possibilities. Evolutionary selection additionally provides diverse adaptive outcomes in a single transition and generally does not result in single fitter types. The totality of heterogeneities in an adapting population increases the chance that at least some individuals meet immediate or future challenges. However, heterogeneity complicates the adaptomics of single transitions, and we propose that subpopulations will need to be integrated into future population biology and systems biology predictions of bacterial behavior.

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Increased Mutation Frequency in Redox-Impaired Escherichia coli Due to RelA- and RpoS-Mediated Repression of DNA Repair

Cited by 6 publications

References 79 publications

Genome-Wide Mapping of Furfural Tolerance Genes in Escherichia coli

Genome-Wide Mapping of Furfural Tolerance Genes in Escherichia coli

Genetic and chemical knockdown: a complementary strategy for evaluating an anti-infective target

Culture History and Population Heterogeneity as Determinants of Bacterial Adaptation: the Adaptomics of a Single Environmental Transition

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