Lethal mutagenesis of bacteria.
Open accessAbstract
Lethal mutagenesis, the killing of a microbial pathogen with a chemical mutagen, is a potential broad-spectrum antiviral treatment. It operates by raising the genomic mutation rate to the point that the deleterious load causes the population to decline. Its use has been limited to RNA viruses because of their high intrinsic mutation rates. Microbes with DNA genomes, which include many viruses and bacteria, have not been considered for this type of treatment because their low intrinsic mutation rates seem difficult to elevate enough to cause extinction. Surprisingly, models of lethal mutagenesis indicate that bacteria may be candidates for lethal mutagenesis. In contrast to viruses, bacteria reproduce by binary fission, and this property ensures their extinction if subjected to a mutation rate >0.69 deleterious mutations per generation. The extinction threshold is further lowered when bacteria die from environmental causes, such as washout or host clearance. In practice, mutagenesis can require many generations before extinction is achieved, allowing the bacterial population to grow to large absolute numbers before the load of deleterious mutations causes the decline. Therefore, if effective treatment requires rapid population decline, mutation rates ≫0.69 may be necessary to achieve treatment success. Implications for the treatment of bacteria with mutagens, for the evolution of mutator strains in bacterial populations, and also for the evolution of mutation rate in cancer are discussed.
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The origin of their conclusion is the existence of nonzero degradation rate, initiated by the first equation in Eq. (60).
“The origin of their conclusion is the existence of nonzero degradation rate , initiated by the first equation in Eq.(60).”
From Lethal mutants and truncated selection together solve a paradox of the origin of life (2011) · cites this paper as [37]
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The emergence of a birth-dependent mutation rate in asexuals: causes and consequencesPreprint
Patout, F., Forien, R., Alfaro, M., Papaix, J. J., & Roques, L. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.06.11.448026 · Cited by 2 · see citing works
“This includes lethal mutagenesis theory (Bull et al., 2007; Bull and Wilke, 2008), where too high mutation rates may lead to extinction, evolutionary rescue (Anciaux et al., 2019) or the invasion of a sink (Lavigne et al., 2020).”
BackgroundEvolutionary adaptation is facilitated by the presence of lethal genotypes
Blavatska, V., & Waclaw, B. (2024) · Physical Review Research · doi:10.1103/physrevresearch.6.013286 · Cited by 1 · see citing works
Nonlethal Fraction of Virus Population in Evolution Models with Lethal Mutations
Yakushkina, T., & Saakian, D. B. (2017) · Journal of the Physical Society of Japan · doi:10.7566/jpsj.86.034801 · Cited by 1 · see citing works
The evolution of a high mutation rate and declining fitness in asexual populations
Gentile, C. F. (2012) · ScholarlyCommons (University of Pennsylvania) · Cited by 1 · see citing works
Evolution at a high imposed mutation rate
Wilcox, A. (2017) · Nottingham Trent University's Institutional Repository (Nottingham Trent Repository) · Cited by 1 · see citing works
Khafaji, K. A. A., & Thwami, A. N. A. (2011) · Journal of Biotechnology Research Center · doi:10.24126/jobrc.2011.5.1.149
The emergence of a birth-dependent mutation rate: causes and consequencesPreprint
Patout, F., Forien, R., Alfaro, M., Papaix, J. J., & Roques, L. (2021) · arXiv (Cornell University) · doi:10.48550/arxiv.2101.01923
“mutagenesis theory (Bull et al., 2007; Bull and Wilke, 2008), where too high mutation rates may lead to extinction, evolutionary rescue (Anciaux et al.”
BackgroundFaculty Opinions recommendation of Mutation bias and GC content shape antimutator invasions.
Baer, C. F. (2019) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.736206413.793564154
Lynch, M. (2024) · Oxford University Press eBooks · doi:10.1093/oso/9780192847287.003.0002
Anciaux, Y. (2017) · doi:10.70675/5387bd7fz8e12z4e7fz9f49z1ae5f8b846b4
“Lethal mutagenesis has been investigated empirically for treatment against viruses (Springman et al. 2010), bacteria (Bull and Wilke 2008) or cancer cells (Liu et al. 2015).”
- Authors
- Bull, J. J., & Wilke, C. O.
- Affiliations
- The University of Texas at Austin (US)
- Corresponding author
- Wilke, Claus O
- Venue
- Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2008-10-01
- Volume
- 180
- Issue
- 2
- Pages
- 1061-1070
- ISSN
- 0016-6731 (ISSN-L)
- 1943-2631
- PMC
- PMC2567356
- OpenAlex
- W2116887235
- Cited by
- 48
- References
- 57
- Citations by year
- 2025: 1 · 2024: 4 · 2023: 1 · 2021: 3 · 2020: 2 · 2019: 5 · 2018: 3 · 2017: 7 · 2015: 1 · 2013: 2 · 2012: 4
- FWCI
- 2.86
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Genetics (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of General Medical Sciences (R01GM057756, R01 GM57756)
- National Institute of Allergy and Infectious Diseases (R01AI065960)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
- Physical Sciences › Environmental Science › Ecology › Bacteriophages and microbial interactions
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Mathematical and Theoretical Epidemiology and Ecology Models
- Keywords
- lethal mutagenesis, bacterial mutagenesis, chemical mutagens, deleterious mutation load, binary fission, mutator strains, mutation rate evolution
- MeSH terms
- Bacteria, DNA Repair, Mutagens, Mutation, Mutagenesis, Evolution, Molecular, Drug Resistance, Bacterial
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