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Antimicrobial Agents and Chemotherapy, December 2007, p. 4267-4275, Vol. 51, No. 12
0066-4804/07/$08.00+0     doi:10.1128/AAC.00962-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Frequency of Development and Associated Physiological Cost of Azithromycin Resistance in Chlamydia psittaci 6BC and C. trachomatis L2{triangledown}

Rachel Binet and Anthony T. Maurelli*

Department of Microbiology and Immunology, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, Maryland 20814-4799

Received 25 July 2007/ Returned for modification 28 August 2007/ Accepted 25 September 2007

Azithromycin is a major drug used in the treatment and prophylaxis of chlamydial infections. Spontaneous azithromycin-resistant mutants of Chlamydia psittaci 6BC were isolated in vitro in the plaque assay at a frequency of about 10–8. Isogenic clonal variants with A2058C, A2059G, or A2059C mutations in the unique 23S rRNA gene (Escherichia coli numbering system) displayed MICs for multiple macrolides (i.e., azithromycin, erythromycin, josamycin, and spiramycin) at least 100 times higher than those of the parent strain and were also more resistant to the lincosamide clindamycin. Chlamydia trachomatis L2 variants with a Gln-to-Lys substitution in ribosomal protein L4 at position 66 (E. coli numbering system), conferring an eightfold decrease in azithromycin and erythromycin sensitivities and a fourfold decrease in josamycin and spiramycin sensitivities, were isolated following serial passage in subinhibitory concentrations of azithromycin. Each mutation was stably maintained in the absence of selection but severely affected chlamydial infectivity, as determined by monitoring the development of each isolate over 46 h in the absence of selection, in pure culture or in 1:1 competition with the isogenic parent. Data in this study support the hypothesis that the mechanisms which confer high-level macrolide resistance in chlamydiae carry a prohibitive physiological cost and may thus limit the emergence of highly resistant clones of these important pathogens in vivo.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814-4799. Phone: (301) 295-3415. Fax: (301) 295-1545. E-mail: amaurelli{at}usuhs.mil

{triangledown} Published ahead of print on 1 October 2007.

Antimicrobial Agents and Chemotherapy, December 2007, p. 4267-4275, Vol. 51, No. 12
0066-4804/07/$08.00+0     doi:10.1128/AAC.00962-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Binet, R., Maurelli, A. T. (2009). Transformation and isolation of allelic exchange mutants of Chlamydia psittaci using recombinant DNA introduced by electroporation. Proc. Natl. Acad. Sci. USA 106: 292-297 [Abstract] [Full Text]  


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