AAC Accepts, published online ahead of print on 1 October 2007

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Antimicrob. Agents Chemother. doi:10.1128/AAC.00962-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

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

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, MD 20814-4799

^* To whom correspondence should be addressed. Email: amaurelli{at}usuhs.mil.

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 the parent strain and were also more resistant to the lincosamide clindamycin. C. trachomatis L2 variants with a Gln to Lys substitution in ribosomal protein L4 at position 66 (E. coli numbering system) conferring an eight-fold decrease in azithromycin and erythromycin sensitivities and a four-fold 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 following the development of each isolate over 46 hours in the absence of selection, in pure culture or in 1:1 competition with the isogenic parent. Data provided 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.

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]