Rifalazil pretreatment of mammalian cell cultures prevents subsequent Chlamydia infection.
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 microg/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.
Suchland
Robert J
RJ
Division of Infectious Diseases, Department of Medicine, University of Washington, Seattle, WA 98195, USA.
Brown
Kara
K
Rothstein
David M
DM
Stamm
Walter E
WE
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002460:Cell Line; D002689:Chlamydia / Q000187:drug effects* / Q000254:growth & development; D002690:Chlamydia Infections / Q000517:prevention & control; D006801:Humans; D008826:Microbial Sensitivity Tests; D012008:Recurrence; D012294:Rifamycins / Q000494:pharmacology*; D013997:Time Factors
D000900:Anti-Bacterial Agents; D012294:Rifamycins; C068980:KRM 1648