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Fitness of antibiotic-resistant microorganisms and compensatory mutations

Nature Medicine volume 4, pages 1343–1344 (1998)Cite this article

To the editor—The increasingly widespread use of antibiotics during the past decade has led to an alarming upsurge in antibiotic-resistant bacteria. The persistence of strains with chromosomal resistance has been observed many times. Restrictions on the use of antibiotics have been advocated not only to contain the dissemination of resistance but also to favor the disappearance of the resistant bacteria already present in human and environmental reservoirs1,2,3. Implicit in these strategies is that resistance to antibiotics reduces the fitness of bacteria (the 'cost' of resistance), allowing sensitive bacteria to replace resistant strains in a drug-free environment. In fact, it has been observed that drug-resistant bacterial pathogens with attenuated fitness rapidly accumulated various types of compensatory mutations that restored fitness without altering the level of bacterial resistance4,5.

Several point mutations at amino acid 42 in the rpsL genes of Escherichia coli and Salmonella typhimurium confer resistance to high concentrations of streptomycin. The streptomycin-resistant mutants can be classified into restrictive and non-restrictive classes with respect to their translation fidelity6. The restrictive mutations show attenuated virulence, whereas non-restrictive resistance mutations have unaltered virulence properties, as determined experimentally in an in vivo model4. Mutants belonging to the restrictive class were used to demonstrate that compensatory mutations developed rapidly both in vitro and in vivo. The compensatory mutations increased the rate of peptide chain elongation and restored virulence4,5. We now provide evidence that selection for chromosomally fixed, drug-resistance-mediating mutations that confer this reduced fitness is likely to represent an in vitro phenomenon but may not be observed in vivo.

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  1. Institut für Medizinische Mikrobiologie Medizinische Hochschule Hannover, Hannover, 30625, Germany

    Erik C. Böttger, Burkhard Springer, Michel Pletschette & Peter Sander

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  1. Erik C. Böttger
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  4. Peter Sander
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Böttger, E., Springer, B., Pletschette, M. et al. Fitness of antibiotic-resistant microorganisms and compensatory mutations. Nat Med 4, 1343–1344 (1998). https://doi.org/10.1038/3906

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