This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Sander, P.
Right arrow Articles by Böttger, E. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sander, P.
Right arrow Articles by Böttger, E. C.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, May 2002, p. 1204-1211, Vol. 46, No. 5
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.5.1204-1211.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Fitness Cost of Chromosomal Drug Resistance-Conferring Mutations

Peter Sander,1,2* Burkhard Springer,2 Therdsak Prammananan,2,{dagger} Antje Sturmfels,2 Martin Kappler,3 Michel Pletschette,2 and Erik C. Böttger1,2

Institut für Medizinische Mikrobiologie, Universität Zürich, CH-8028 Zürich, Switzerland,1 Institut für Medizinische Mikrobiologie,2 Institut für Biometrie, Medizinische Hochschule Hannover, 30625 Hannover, Germany3

Received 21 August 2001/ Returned for modification 27 November 2001/ Accepted 24 January 2002

To study the cost of chromosomal drug resistance mutations to bacteria, we investigated the fitness cost of mutations that confer resistance to different classes of antibiotics affecting bacterial protein synthesis (aminocyclitols, 2-deoxystreptamines, macrolides). We used a model system based on an in vitro competition assay with defined Mycobacterium smegmatis laboratory mutants; selected mutations were introduced by genetic techniques to address the possibility that compensatory mutations ameliorate the resistance cost. We found that the chromosomal drug resistance mutations studied often had only a small fitness cost; compensatory mutations were not involved in low-cost or no-cost resistance mutations. When drug resistance mutations found in clinical isolates were considered, selection of those mutations that have little or no fitness cost in the in vitro competition assay seems to occur. These results argue against expectations that link decreased levels of antibiotic consumption with the decline in the level of resistance.

* Corresponding author. Mailing address: Institut für Medizinische Mikrobiologie, Universität Zürich, Gloriastr. 30/32, CH-8028 Zürich, Switzerland. Phone: 41-1-634 2684. Fax: 41-1-634 4906. E-mail: psander{at}immv.unizh.ch.

{dagger} Present address: Division of Mycology and Mycobacteriology, Department of Microbiology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.

Antimicrobial Agents and Chemotherapy, May 2002, p. 1204-1211, Vol. 46, No. 5
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.5.1204-1211.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Sundqvist, M., Geli, P., Andersson, D. I., Sjolund-Karlsson, M., Runehagen, A., Cars, H., Abelson-Storby, K., Cars, O., Kahlmeter, G. (2009). Little evidence for reversibility of trimethoprim resistance after a drastic reduction in trimethoprim use. J Antimicrob Chemother 0: dkp387v1-dkp387 [Abstract] [Full Text]  
  • Paulander, W., Maisnier-Patin, S., Andersson, D. I. (2009). The Fitness Cost of Streptomycin Resistance Depends on rpsL Mutation, Carbon Source and RpoS ({sigma}S). Genetics 183: 539-546 [Abstract] [Full Text]  
  • Luciani, F., Sisson, S. A., Jiang, H., Francis, A. R., Tanaka, M. M. (2009). The epidemiological fitness cost of drug resistance in Mycobacterium tuberculosis. Proc. Natl. Acad. Sci. USA 106: 14711-14715 [Abstract] [Full Text]  
  • Springer, B., Calligaris-Maibach, R. C., Ritter, C., Bottger, E. C. (2008). Tuberculosis Drug Resistance in an Area of Low Endemicity in 2004 to 2006: Semiquantitative Drug Susceptibility Testing and Genotyping. J. Clin. Microbiol. 46: 4064-4067 [Abstract] [Full Text]  
  • Binet, R., Maurelli, A. T. (2007). Frequency of Development and Associated Physiological Cost of Azithromycin Resistance in Chlamydia psittaci 6BC and C. trachomatis L2. Antimicrob. Agents Chemother. 51: 4267-4275 [Abstract] [Full Text]  
  • Walk, S. T., Mladonicky, J. M., Middleton, J. A., Heidt, A. J., Cunningham, J. R., Bartlett, P., Sato, K., Whittam, T. S. (2007). Influence of Antibiotic Selection on Genetic Composition of Escherichia coli Populations from Conventional and Organic Dairy Farms. Appl. Environ. Microbiol. 73: 5982-5989 [Abstract] [Full Text]  
  • Warner, D. F., Mizrahi, V. (2006). Tuberculosis Chemotherapy: the Influence of Bacillary Stress and Damage Response Pathways on Drug Efficacy. Clin. Microbiol. Rev. 19: 558-570 [Abstract] [Full Text]  
  • Gagneux, S., Long, C. D., Small, P. M., Van, T., Schoolnik, G. K., Bohannan, B. J. M. (2006). The competitive cost of antibiotic resistance in Mycobacterium tuberculosis.. Science 312: 1944-1946 [Abstract] [Full Text]  
  • Binet, R., Maurelli, A. T. (2005). Fitness Cost Due to Mutations in the 16S rRNA Associated with Spectinomycin Resistance in Chlamydia psittaci 6BC. Antimicrob. Agents Chemother. 49: 4455-4464 [Abstract] [Full Text]  
  • Meacci, F., Orru, G., Iona, E., Giannoni, F., Piersimoni, C., Pozzi, G., Fattorini, L., Oggioni, M. R. (2005). Drug Resistance Evolution of a Mycobacterium tuberculosis Strain from a Noncompliant Patient. J. Clin. Microbiol. 43: 3114-3120 [Abstract] [Full Text]  
  • Pfister, P., Corti, N., Hobbie, S., Bruell, C., Zarivach, R., Yonath, A., Bottger, E. C. (2005). 23S rRNA base pair 2057-2611 determines ketolide susceptibility and fitness cost of the macrolide resistance mutation 2058A->G. Proc. Natl. Acad. Sci. USA 102: 5180-5185 [Abstract] [Full Text]  
  • Besier, S., Ludwig, A., Brade, V., Wichelhaus, T. A. (2005). Compensatory Adaptation to the Loss of Biological Fitness Associated with Acquisition of Fusidic Acid Resistance in Staphylococcus aureus. Antimicrob. Agents Chemother. 49: 1426-1431 [Abstract] [Full Text]  
  • Luo, N., Pereira, S., Sahin, O., Lin, J., Huang, S., Michel, L., Zhang, Q. (2005). Enhanced in vivo fitness of fluoroquinolone-resistant Campylobacter jejuni in the absence of antibiotic selection pressure. Proc. Natl. Acad. Sci. USA 102: 541-546 [Abstract] [Full Text]  
  • Mariam, D. H., Mengistu, Y., Hoffner, S. E., Andersson, D. I. (2004). Effect of rpoB Mutations Conferring Rifampin Resistance on Fitness of Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 48: 1289-1294 [Abstract] [Full Text]  
  • Sjolund, M., Wreiber, K., Andersson, D. I., Blaser, M. J., Engstrand, L. (2003). Long-Term Persistence of Resistant Enterococcus Species after Antibiotics To Eradicate Helicobacter pylori. ANN INTERN MED 139: 483-487 [Abstract] [Full Text]  
  • Gustafsson, I., Cars, O., Andersson, D. I. (2003). Fitness of antibiotic resistant Staphylococcus epidermidis assessed by competition on the skin of human volunteers. J Antimicrob Chemother 52: 258-263 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»