The DOI matches its Crossref record; 18 of the 18 references it cites were found in a registry or an index.
Adaptation to the fitness costs of antibiotic resistance in Escherichia coli
Open accessAbstract
Policies aimed at alleviating the growing problem of drug-resistant pathogens by restricting antimicrobial usage implicitly assume that resistance reduces the Darwinian fitness of pathogens in the absence of drugs. While fitness costs have been demonstrated for bacteria and viruses resistant to some chemotherapeutic agents, these costs are anticipated to decline during subsequent evolution. This has recently been observed in pathogens as diverse as HIV and Escherichia coli. Here we present evidence that these gentic adaptations to the costs of resistance can virtually preclude resistant lineages from reverting to sensitivity. We show that second site mutations which compensate for the substantial (14 and 18% per generation) fitness costs of streptomycin resistant (rpsL) mutations in E. coli create a genetic background in which streptomycin sensitive, rpsL+ alleles have a 4-30% per generation selective disadvantage relative to adapted, resistant strains. We also present evidence that similar compensatory mutations have been fixed in long-term streptomycin-resistant laboratory strains of E. coli and may account for the persistence of rpsL streptomycin resistance in populations maintained for more than 10,000 generations in the absence of the antibiotic. We discuss the public health implications of these and other experimental results that question whether the more prudent use of antimicrobial chemotherapy will lead to declines in the incidence of drug-resistant pathogenic microbes.
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Cites
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The Population Genetics of Antibiotic Resistance
Levin, B. R., Lipsitch, M., Perrot, V., Schrag, S., Antia, R., Simonsen, L., Moore Walker, N., & Stewart, F. M. (1997) · Clinical Infectious Diseases · doi:10.1093/clinids/24.supplement_1.s9 · Cited by 314
Self-citationReducing antibiotic resistance
Schrag, S. J., & Perrot, V. (1996) · Nature · doi:10.1038/381120b0 · Cited by 254
Self-citation
Cited by
Blount, Z. D., Borland, C. Z., & Lenski, R. E. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0803151105 · Cited by 840
Understanding quantitative genetic variation
Barton, N. H., & Keightley, P. D. (2002) · Nature Reviews Genetics · doi:10.1038/nrg700 · Cited by 835
Variation in immune defence as a question of evolutionary ecology
Schmid-Hempel, P. (2003) · Proceedings of the Royal Society of London. Series B: Biological Sciences · doi:10.1098/rspb.2002.2265 · Cited by 722
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Metadata
- Authors
- Schrag, S. J., Perrot, V., & Levin, B. R.
- Venue
- Proceedings of the Royal Society of London. Series B: Biological Sciences
- Publisher
- The Royal Society
- Published
- 1997-09-22
- Volume
- 264
- Issue
- 1386
- Pages
- 1287-1291
- ISSN
- 0080-4649 (ISSN-L)
- 0962-8452
- 1471-2954
- OpenAlex
- W2121444224
- Cited by
- 396
- References
- 18
- FWCI
- 5.48
- Type
- journal article
- Language
- en
- Open access
- green
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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