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Cited by 417Evolution and Genetic DynamicsAntibiotic Resistance in BacteriaAntimicrobial Resistance in Staphylococcus

The emergence of antibiotic resistance by mutation

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Woodford, N., Ellington, M.J.·2007·Clinical Microbiology and Infection
DOI 10.1111/j.1469-0691.2006.01492.x
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Abstract

The emergence of mutations in nucleic acids is one of the major factors underlying evolution, providing the working material for natural selection. Most bacteria are haploid for the vast majority of their genes and, coupled with typically short generation times, this allows mutations to emerge and accumulate rapidly, and to effect significant phenotypic changes in what is perceived to be real-time. Not least among these phenotypic changes are those associated with antibiotic resistance. Mechanisms of horizontal gene spread among bacterial strains or species are often considered to be the main mediators of antibiotic resistance. However, mutational resistance has been invaluable in studies of bacterial genetics, and also has primary clinical importance in certain bacterial species, such as Mycobacterium tuberculosis and Helicobacter pylori, or when considering resistance to particular antibiotics, especially to synthetic agents such as fluoroquinolones and oxazolidinones. In addition, mutation is essential for the continued evolution of acquired resistance genes and has, e.g., given rise to over 100 variants of the TEM family of beta-lactamases. Hypermutator strains of bacteria, which have mutations in genes affecting DNA repair and replication fidelity, have elevated mutation rates. Mutational resistance emerges de novo more readily in these hypermutable strains, and they also provide a suitable host background for the evolution of acquired resistance genes in vitro. In the clinical setting, hypermutator strains of Pseudomonas aeruginosa have been isolated from the lungs of cystic fibrosis patients, but a more general role for hypermutators in the emergence of clinically relevant antibiotic resistance in a wider variety of bacterial pathogens has not yet been proven.

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Crossref · 10.1111/j.1469-0691.2006.01492.x

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  • Hypermutator phenotypes resulting from mutations in DNA repair genes have been proposed to precede the appearance of resistance in bacteria.

    “Furthermore, the appearance of ‘hypermutator phenotypes’ resulting from mutations in DNA repair genes has been proposed to precede the appearance of resistance in bacteria [133].”

    From Evolutionary Emergence of Drug Resistance in Candida Opportunistic Pathogens (2018) · cites this paper as [133]

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Authors
Woodford, N., & Ellington, M. J.
Affiliations
Health Protection Agency (GB)
Corresponding author
Woodford, N.
ORCID
Venue
Clinical Microbiology and Infection
Publisher
Elsevier BV
Published
2007-01
Volume
13
Issue
1
Pages
5-18
ISSN
1198-743X (ISSN-L)
DOI
10.1111/j.1469-0691.2006.01492.x
OpenAlex
W1608826984
Cited by
417
References
174
Citations by year
2026: 26 · 2025: 26 · 2024: 45 · 2023: 37 · 2022: 36 · 2021: 42 · 2020: 31 · 2019: 26 · 2018: 24 · 2017: 23 · 2016: 7 · 2015: 12 · 2014: 13 · 2013: 6 · 2012: 8
FWCI
1.25
Type
journal article
Language
en
Open access
Licence
Locations
  • Clinical Microbiology and Infection (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Antibiotic Resistance in Bacteria
  • Health Sciences › Medicine › Infectious Diseases › Antimicrobial Resistance in Staphylococcus
Keywords
antibiotic resistance, bacterial mutation, DNA repair, replication fidelity, TEM beta-lactamase, fluoroquinolone resistance, oxazolidinone resistance, horizontal gene transfer, Mycobacterium tuberculosis, Helicobacter pylori, Pseudomonas aeruginosa, cystic fibrosis, bacterial evolution
MeSH terms
Anti-Bacterial Agents, Bacteria, Drug Resistance, Biological Evolution, Genes, Bacterial, Mutation

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