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Mutation frequency and biological cost of antibiotic resistance in Helicobacter pylori
Open accessAbstract
Among the several factors that affect the appearance and spread of acquired antibiotic resistance, the mutation frequency and the biological cost of resistance are of special importance. Measurements of the mutation frequency to rifampicin resistance in Helicobacter pylori strains isolated from dyspeptic patients showed that ≈1/4 of the isolates had higher mutation frequencies than Enterobacteriaceae mismatch-repair defective mutants. This high mutation frequency could explain why resistance is so frequently acquired during antibiotic treatment of H. pylori infections. Inactivation of the mutS gene had no substantial effect on the mutation frequency, suggesting that MutS-dependent mismatch repair is absent in this bacterium. Furthermore, clarithromycin resistance conferred a biological cost, as measured by a decreased competitive ability of the resistant mutants in mice. In clinical isolates this cost could be reduced, indicating that compensation is a clinically relevant phenomenon that could act to stabilize resistant bacteria in a population.
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Cited by
Wu, M., Sun, L. V., Vamathevan, J., Riegler, M., Deboy, R., Brownlie, J. C., McGraw, E. A., Martin, W., Esser, C., Ahmadinejad, N., et al. (2004) · PLoS Biology · doi:10.1371/journal.pbio.0020069 · Cited by 851
“…without high evolutionary rates have lost some of the same pathways lost in intracellular species, while many free-living species have lost key pathways resulting in high mutation rates (e.g., Helicobacter pylori has apparently lost mismatch repair [Eisen1997, Eisen 1998b; Bjorkholm et al. 2001]).”
The fitness costs of antibiotic resistance mutations
Melnyk, A. H., Wong, A., & Kassen, R. (2015) · Evolutionary Applications · doi:10.1111/eva.12196 · Cited by 689
The Competitive Cost of Antibiotic Resistance in Mycobacterium tuberculosis
Gagneux, S., Long, C. D., Small, P. M., Van, T., Schoolnik, G. K., & Bohannan, B. J. M. (2006) · Science · doi:10.1126/science.1124410 · Cited by 627
Natural Products as Platforms To Overcome Antibiotic Resistance
Rossiter, S. E., Fletcher, M. H., & Wuest, W. M. (2017) · Chemical Reviews · doi:10.1021/acs.chemrev.7b00283 · Cited by 622
Stress-Induced Mutagenesis in Bacteria
Bjedov, I., Tenaillon, O., Gérard, B., Souza, V., Denamur, E., Radman, M., Taddei, F., & Matic, I. (2003) · Science · doi:10.1126/science.1082240 · Cited by 587
Metadata
- Authors
- Björkholm, B., Sjölund, M., Falk, P. G., Berg, O. G., Engstrand, L., & Andersson, D. I.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2001-11-20
- Volume
- 98
- Issue
- 25
- Pages
- 14607-14612
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2075476726
- Cited by
- 404
- References
- 0
- FWCI
- 14.90
- Type
- journal article
- Language
- en
- Open access
- green
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- Björkholm, B., Sjölund, M., Falk, P. G., Berg, O. G., Engstrand, L., & Andersson, D. I. (2001). Mutation frequency and biological cost of antibiotic resistance in Helicobacter pylori. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.241517298
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