Mutation rate plasticity in rifampicin resistance depends on Escherichia coli cell-cell interactions.
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Variation of mutation rate at a particular site in a particular genotype, in other words mutation rate plasticity (MRP), can be caused by stress or ageing. However, mutation rate control by other factors is less well characterized. Here we show that in wild-type Escherichia coli (K-12 and B strains), the mutation rate to rifampicin resistance is plastic and inversely related to population density: lowering density can increase mutation rates at least threefold. This MRP is genetically switchable, dependent on the quorum-sensing gene luxS--specifically its role in the activated methyl cycle--and is socially mediated via cell-cell interactions. Although we identify an inverse association of mutation rate with fitness under some circumstances, we find no functional link with stress-induced mutagenesis. Our experimental manipulation of mutation rates via the social environment raises the possibility that such manipulation occurs in nature and could be exploited medically.
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For the two experiments from Krašovec et al. (2014), the relative fitness values are w1 = 1.47 and w2 = 1.45, and the final cell numbers are Nt,1 = 2.27 × 10^8 and Nt,2 = 5.15 × 10^8.
“The investigators measured the relative fitness in both experiments and obtained w1 = 1.47 and w2 = 1.45. They also measured the two Nt values: Nt,1 = 2.27 × 108 and Nt,2 = 5.15 × 108.”
From rSalvador: An R Package for the Fluctuation Experiment (2017) · cites this paper as Krašovec et al. (2014)
The Methods sections ‘Fitness assay’ and ‘Fluctuation tests’ say the investigators calculated relative fitness and measured final viable-cell numbers (Nt). Our copy does not report the claimed pairs of values—1.47 and 1.45, or 2.27 × 10^8 and 5.15 × 10^8—so it does not verify those numbers. (LLM, conf=0.86)
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- Authors
- Krašovec, R., Belavkin, R. V., Aston, J. A. D., Channon, A., Aston, E., Rash, B. M., Kadirvel, M., Forbes, S., & Knight, C. G.
- Affiliations
- University of Manchester (GB)
- Middlesex University London (GB)
- University of Cambridge (GB)
- Keele University (GB)
- Corresponding author
- Krašovec, Rok
- ORCID
- Venue
- Nature Communications
- Published
- 2014-04-29
- Volume
- 5
- Issue
- 1
- Pages
- 3742-3742
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC4007418
- OpenAlex
- W2145625676
- Cited by
- 85
- References
- 51
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 5 · 2023: 6 · 2022: 4 · 2021: 7 · 2020: 12 · 2019: 11 · 2018: 6 · 2017: 8 · 2016: 6 · 2015: 5 · 2014: 4
- FWCI
- 5.02
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion, cc-by)
- Warwick Research Archive Portal (University of Warwick) (acceptedVersion)
- SHURA (Sheffield Hallam University Research Archive) (Sheffield Hallam University) (acceptedVersion)
- Keele Research Repository (Keele University) (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- Middlesex University Research Repository (Middlesex University Of London) (submittedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion, cc-by)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion, other-oa)
- Funders
- Wellcome Trust (082453/Z/07/Z, 082453)
- Cancer Research UK (16465, 18097)
- Directorate for Biological Sciences
- Engineering and Physical Sciences Research Council (EP/K021672/2, EP/H031936/1, EP/K021672/1)
- Biotechnology and Biological Sciences Research Council (BB/L009579/1)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bacterial biofilms and quorum sensing
- Keywords
- rifampicin resistance, Escherichia coli, cell-cell interactions, quorum sensing, LuxS, population density, stress-induced mutagenesis, fitness, social environment, antibiotic resistance
- MeSH terms
- Analysis of Variance, Bacterial Proteins, Escherichia coli, Population Density, Rifampin, Carbon-Sulfur Lyases, Genetic Variation, DNA Primers, Drug Resistance, Bacterial, Genetic Fitness, Microbial Interactions, Mutation Rate, Real-Time Polymerase Chain Reaction
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