scholarly journals Opposing effects of population density and stress on Escherichia coli mutation rate

2018 ◽  
Author(s):  
Rok Krašovec ◽  
Huw Richards ◽  
Danna R. Gifford ◽  
Roman V. Belavkin ◽  
Alastair Channon ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Population Density ◽  
Mutation Rate ◽  
Ecological Factors ◽  
Rich Media ◽  
Rate Minimum ◽  
Induced Mutagenesis ◽  
Opposing Effects ◽  
Relationship Of ◽  
Opposing Effect

AbstractEvolution depends on mutations. For an individual genotype, the rate at which mutations arise is known to increase with various stressors (stress-induced mutagenesis – SIM) and decrease at high population density (density-associated mutation-rate plasticity – DAMP). We hypothesised that these two forms of mutation rate plasticity would have opposing effects across a nutrient gradient. Here we test this hypothesis, culturing Escherichia coli bacteria in increasingly rich media. We distinguish an increase in mutation rate with added nutrients through SIM (dependent on error-prone polymerases Pol IV and Pol V) and an opposing effect of DAMP (dependent on MutT, which removes oxidised G nucleotides). The combination of DAMP and SIM result in a mutation rate minimum at intermediate nutrient levels (which can support 7×108 cells ml−1). These findings demonstrate a strikingly close and nuanced relationship of ecological factors – stress and population density – with mutation, the fuel of all evolution.

scholarly journals Opposing effects of final population density and stress on Escherichia coli mutation rate

2018 ◽  
Vol 12 (12) ◽  
pp. 2981-2987
Author(s):  
Rok Krašovec ◽  
Huw Richards ◽  
Danna R. Gifford ◽  
Roman V. Belavkin ◽  
Alastair Channon ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Population Density ◽  
Mutation Rate ◽  
Final Population ◽  
Opposing Effects

scholarly journals L-Alanine Prototrophic Suppressors Emerge from L-Alanine Auxotroph through Stress-Induced Mutagenesis in Escherichia coli

2021 ◽  
Vol 9 (3) ◽  
pp. 472
Author(s):  
Harutaka Mishima ◽  
Hirokazu Watanabe ◽  
Kei Uchigasaki ◽  
So Shimoda ◽  
Shota Seki ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Pyruvate Dehydrogenase ◽  
Pyruvate Dehydrogenase Complex ◽  
Spontaneous Mutation ◽  
Point Mutations ◽  
Whole Genome Analysis ◽  
E Coli ◽  
Clone Pair ◽  
Induced Mutagenesis ◽  
Isogenic Mutants

In Escherichia coli, L-alanine is synthesized by three isozymes: YfbQ, YfdZ, and AvtA. When an E. coli L-alanine auxotrophic isogenic mutant lacking the three isozymes was grown on L-alanine-deficient minimal agar medium, L-alanine prototrophic mutants emerged considerably more frequently than by spontaneous mutation; the emergence frequency increased over time, and, in an L-alanine-supplemented minimal medium, correlated inversely with L-alanine concentration, indicating that the mutants were derived through stress-induced mutagenesis. Whole-genome analysis of 40 independent L-alanine prototrophic mutants identified 16 and 18 clones harboring point mutation(s) in pyruvate dehydrogenase complex and phosphotransacetylase-acetate kinase pathway, which respectively produce acetyl coenzyme A and acetate from pyruvate. When two point mutations identified in L-alanine prototrophic mutants, in pta (D656A) and aceE (G147D), were individually introduced into the original L-alanine auxotroph, the isogenic mutants exhibited almost identical growth recovery as the respective cognate mutants. Each original- and isogenic-clone pair carrying the pta or aceE mutation showed extremely low phosphotransacetylase or pyruvate dehydrogenase activity, respectively. Lastly, extracellularly-added pyruvate, which dose-dependently supported L-alanine auxotroph growth, relieved the L-alanine starvation stress, preventing the emergence of L-alanine prototrophic mutants. Thus, L-alanine starvation-provoked stress-induced mutagenesis in the L-alanine auxotroph could lead to intracellular pyruvate increase, which eventually induces L-alanine prototrophy.

scholarly journals Geo-Spatial Analysis of Population Density and Annual Income to Identify Large-Scale Socio-Demographic Disparities

2021 ◽  
Vol 10 (7) ◽  
pp. 432
Author(s):  
Nicolai Moos ◽  
Carsten Juergens ◽  
Andreas P. Redecker
Keyword(s):  
Population Density ◽  
Large Scale ◽  
Methodological Approach ◽  
Spatial Relationship ◽  
Postal Code ◽  
Annual Income ◽  
Choropleth Maps ◽  
Clustering Approach ◽  
Relationship Of ◽  
Insight Into

This paper describes a methodological approach that is able to analyse socio-demographic and -economic data in large-scale spatial detail. Based on the two variables, population density and annual income, one investigates the spatial relationship of these variables to identify locations of imbalance or disparities assisted by bivariate choropleth maps. The aim is to gain a deeper insight into spatial components of socioeconomic nexuses, such as the relationships between the two variables, especially for high-resolution spatial units. The used methodology is able to assist political decision-making, target group advertising in the field of geo-marketing and for the site searches of new shop locations, as well as further socioeconomic research and urban planning. The developed methodology was tested in a national case study in Germany and is easily transferrable to other countries with comparable datasets. The analysis was carried out utilising data about population density and average annual income linked to spatially referenced polygons of postal codes. These were disaggregated initially via a readapted three-class dasymetric mapping approach and allocated to large-scale city block polygons. Univariate and bivariate choropleth maps generated from the resulting datasets were then used to identify and compare spatial economic disparities for a study area in North Rhine-Westphalia (NRW), Germany. Subsequently, based on these variables, a multivariate clustering approach was conducted for a demonstration area in Dortmund. In the result, it was obvious that the spatially disaggregated data allow more detailed insight into spatial patterns of socioeconomic attributes than the coarser data related to postal code polygons.

Methyl cinnamate derivatives enhance UV-induced mutagenesis due to the inhibition of DNA excision repair in Escherichia coli B/r

1985 ◽  
Vol 146 (1) ◽  
pp. 15-22 ◽  
Author(s):  
Kayoko Shimoi ◽  
Yoshiyuki Nakamura ◽  
Tadataka Noro ◽  
Isao Tomita ◽  
Seigo Fukushima ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Excision Repair ◽  
Methyl Cinnamate ◽  
Dna Excision Repair ◽  
Induced Mutagenesis ◽  
Escherichia Coli B

Metal-induced mutagenesis in the lacI gene of Escherichia coli

1984 ◽  
Vol 126 (1) ◽  
pp. 9-18 ◽  
Author(s):  
R ZAKOUR ◽  
B GLICKMAN
Keyword(s):  
Escherichia Coli ◽  
Laci Gene ◽  
Induced Mutagenesis

scholarly journals Novel Pharmacokinetic/Pharmacodynamic Parameters Quantify the Exposure–Effect Relationship of Levofloxacin against Fluoroquinolone-Resistant Escherichia coli

Antibiotics ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 615
Author(s):  
Johanna Seeger ◽  
Sebastian Guenther ◽  
Katharina Schaufler ◽  
Stefan E. Heiden ◽  
Robin Michelet ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Fluoroquinolone Resistance ◽  
Infection Model ◽  
Bacterial Killing ◽  
Exposure Effect ◽  
Effect Relationship ◽  
Concentration Time ◽  
Antibiotic Effect ◽  
Relationship Of ◽  
Antibiotic Dosing

Minimal inhibitory concentration-based pharmacokinetic/pharmacodynamic (PK/PD) indices are commonly applied to antibiotic dosing optimisation, but their informative value is limited, as they do not account for bacterial growth dynamics over time. We aimed to comprehensively characterise the exposure–effect relationship of levofloxacin against Escherichia coli and quantify strain-specific characteristics applying novel PK/PD parameters. In vitro infection model experiments were leveraged to explore the exposure–effect relationship of three clinical Escherichia coli isolates, harbouring different genomic fluoroquinolone resistance mechanisms, under constant levofloxacin concentrations or human concentration–time profiles (≤76 h). As an exposure metric, the ‘cumulative area under the levofloxacin–concentration time curve’ was determined. The antibiotic effect was assessed as the ‘cumulative area between the growth control and the bacterial-killing and -regrowth curve’. PK/PD modelling was applied to characterise the exposure–effect relationship and derive novel PK/PD parameters. A sigmoidal Emax model with an inhibition term best characterised the exposure–effect relationship and allowed for discrimination between two isolates sharing the same MIC value. Strain- and exposure-pattern-dependent differences were captured by the PK/PD parameters and elucidated the contribution of phenotypic adaptation to bacterial regrowth. The novel exposure and effect metrics and derived PK/PD parameters allowed for comprehensive characterisation of the isolates and could be applied to overcome the limitations of the MIC in clinical antibiotic dosing decisions, drug research and preclinical development.

Mutagenesis and More: umuDC and the Escherichia coli SOS Response

Genetics ◽  
1998 ◽  
Vol 148 (4) ◽  
pp. 1599-1610 ◽  
Author(s):  
Bradley T Smith ◽  
Graham C Walker
Keyword(s):  
Escherichia Coli ◽  
Dna Damage ◽  
Cellular Response ◽  
Sos Response ◽  
Posttranslational Regulation ◽  
E Coli ◽  
Sos Mutagenesis ◽  
Induced Mutagenesis ◽  
Mechanistic Basis ◽  
Increase Cell Survival

Abstract The cellular response to DNA damage that has been most extensively studied is the SOS response of Escherichia coli. Analyses of the SOS response have led to new insights into the transcriptional and posttranslational regulation of processes that increase cell survival after DNA damage as well as insights into DNA-damage-induced mutagenesis, i.e., SOS mutagenesis. SOS mutagenesis requires the recA and umuDC gene products and has as its mechanistic basis the alteration of DNA polymerase III such that it becomes capable of replicating DNA containing miscoding and noncoding lesions. Ongoing investigations of the mechanisms underlying SOS mutagenesis, as well as recent observations suggesting that the umuDC operon may have a role in the regulation of the E. coli cell cycle after DNA damage has occurred, are discussed.

scholarly journals Death and population dynamics affect mutation rate estimates and evolvability under stress in bacteria

2017 ◽  
Author(s):  
Antoine Frénoy ◽  
Sebastian Bonhoeffer
Keyword(s):  
Population Dynamics ◽  
Mutation Rate ◽  
Death Rate ◽  
Mutation Rates ◽  
Resistance Mutations ◽  
Bacterial Populations ◽  
Plasmid Segregation ◽  
Genome Wide ◽  
Response To Stress ◽  
Induced Mutagenesis

AbstractThe stress-induced mutagenesis paradigm postulates that in response to stress, bacteria increase their genome-wide mutation rate, in turn increasing the chances that a descendant is able to withstand the stress. This has implications for antibiotic treatment: exposure to sub-inhibitory doses of antibiotics has been reported to increase bacterial mutation rates, and thus probably the rate at which resistance mutations appear and lead to treatment failure.Measuring mutation rates under stress, however, is problematic, because existing methods assume there is no death. Yet sub-inhibitory stress levels may induce a substantial death rate. Death events need to be compensated by extra replication to reach a given population size, thus giving more opportunities to acquire mutations. We show that ignoring death leads to a systematic overestimation of mutation rates under stress.We developed a system using plasmid segregation to measure death and growth rates simultaneously in bacterial populations. We use it to replicate classical experiments reporting antibiotic-induced mutagenesis. We found that a substantial death rate occurs at the tested sub-inhibitory concentrations, and taking this death into account lowers and sometimes removes the signal for stress-induced mutagenesis. Moreover even when antibiotics increase mutation rate, sub-inhibitory treatments do not increase genetic diversity and evolvability, again because of effects of the antibiotics on population dynamics.Beside showing that population dynamic is a crucial but neglected parameter affecting evolvability, we provide better experimental and computational tools to study evolvability under stress, leading to a re-assessment of the magnitude and significance of the stress-induced mutagenesis paradigm.

Sign in / Sign up

Export Citation Format

Share Document