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Antimicrobial Agents and Chemotherapy, November 2009, p. 4604-4611, Vol. 53, No. 11
0066-4804/09/$08.00+0 doi:10.1128/AAC.00477-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

K. M. Sandoz,2,
B. M. Jeffrey,2
W. E. Stamm,1 and
D. D. Rockey2*
Division of Allergy and Infectious Disease, Department of Medicine, University of Washington, Seattle, Washington,1 Department of Biomedical Sciences, Oregon State University, Corvallis, Oregon2
Received 30 March 2009/ Returned for modification 12 June 2009/ Accepted 31 July 2009
There are no examples of stable tetracycline resistance in clinical strains of Chlamydia trachomatis. However, the swine pathogen Chlamydia suis is commonly tetracycline resistant, both in America and in Europe. In tested U.S. strains, this resistance is mediated by a genomic island carrying a tet(C) allele. In the present study, the ability of C. suis to mobilize tet(C) into other chlamydial species was examined. Differently antibiotic resistant strains of C. suis, C. trachomatis, and Chlamydia muridarum were used in coculture experiments to select for multiply antibiotic resistant progeny. Coinfection of mammalian cells with a naturally occurring tetracycline-resistant strain of C. suis and a C. muridarum or C. trachomatis strain containing selected mutations encoding rifampin (rifampicin) or ofloxacin resistance readily produced doubly resistant recombinant clones that demonstrated the acquisition of tetracycline resistance. The resistance phenotype in the progeny from a C. trachomatis L2/oflR-C. suis R19/tetR cross resulted from integration of a 40-kb fragment into a single ribosomal operon of a recipient, leading to a merodiploid structure containing three rRNA operons. In contrast, a cross between C. suis R19/tetR and C. muridarum MoPn/oflR led to a classical double-crossover event transferring 99 kb of DNA from C. suis R19/tetR into C. muridarum MoPn/oflR. Tetracycline resistance was also transferred to recent clinical strains of C. trachomatis. Successful crosses were not obtained when a rifampin-resistant Chlamydophila caviae strain was used as a recipient for crosses with C. suis or C. trachomatis. These findings provide a platform for further exploration of the biology of horizontal gene transfer in Chlamydia while bringing to light potential public health concerns generated by the possibility of acquisition of tetracycline resistance by human chlamydial pathogens.
Published ahead of print on 17 August 2009.
R.J.S. and K.M.S. contributed equally to this project.
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