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Antimicrobial Agents and Chemotherapy, February 2006, p. 439-444, Vol. 50, No. 2
0066-4804/06/$08.00+0     doi:10.1128/AAC.50.2.439-444.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Rifalazil Pretreatment of Mammalian Cell Cultures Prevents Subsequent Chlamydia Infection

Robert J. Suchland,1 Kara Brown,2 David M. Rothstein,2 and Walter E. Stamm1*

Division of Infectious Diseases, Department of Medicine, University of Washington, Seattle, Washington 98195,1 ActivBiotics, Inc., Lexington, Massachusetts 024212

Received 12 August 2005/ Returned for modification 6 September 2005/ Accepted 28 November 2005

Chlamydia species are widely disseminated obligate intracellular pathogens that primarily cause urogenital, ocular, and respiratory infections. In these studies, we show that exposing mammalian cells to antibacterial agents prior to Chlamydia inoculation protects the host cells against subsequent challenge by chlamydiae (the protective effect [PE]). Rifalazil exhibited a considerably stronger PE than did azithromycin, rifampin, doxycycline, and ofloxacin. Specifically, 0.002 µg/ml rifalazil incubated for 1 day with a monolayer of McCoy cells was sufficient to protect against a challenge 2 days later with Chlamydia trachomatis serovar D (UW-3). The PE was observed with five different mammalian cell lines and with a variety of C. trachomatis and Chlamydia pneumoniae isolates. The duration of the PE was 6 to 12 days for rifalazil (depending on the cell line), a maximum of 3 days for azithromycin, and less than a day for the other drugs tested. For rifalazil, the PE was shown to be mediated by inhibition of the chlamydial RNA polymerase since mutants with altered RNA polymerases had correspondingly altered PEs. These results suggest that rifalazil may be unique in its ability to prevent infection with obligate intracellular pathogens for a considerable time after treatment. This characteristic may be of particular public health value in reducing reinfection with chlamydiae.

* Corresponding author. Mailing address: 1959 NE Pacific Street, University of Washington, Box 356523, Seattle, WA 98195. Phone: (206) 616-4170. Fax: (206) 616-4898. E-mail: wes{at}u.washington.edu.

Antimicrobial Agents and Chemotherapy, February 2006, p. 439-444, Vol. 50, No. 2
0066-4804/06/$08.00+0     doi:10.1128/AAC.50.2.439-444.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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