title: Bactericidal activity of first-choice antibiotics against gamma interferon-induced persistent infection of human epithelial cells by Chlamydia trachomatis.
abstract: Chlamydia trachomatis is responsible for clinically important chronic inflammatory diseases of humans, including trachoma and pelvic inflammatory disease. Persistent infection of mucosal sites may contribute to the development of these chronic inflammatory diseases. Standard clinical therapy results in satisfactory cure rates of acute infections; however, chronic infection associated with persistence has been suggested to be less responsive to antibiotic therapy. We report the efficiency of two first-line chlamydial antibiotics, azithromycin and doxycycline, under conditions of eradication of C. trachomatis persistent infection using the in vitro model of gamma interferon (IFN-gamma)-mediated persistence and reactivation from persistence. Doxycycline was superior in eradicating acute (minimal bactericidal concentration [MBC](100) = 2.5 to 5.0 microg/ml) compared to persistent (MBC(100) = 10 to 50 mirog/ml) infection. In contrast, azithromycin was significantly more effective in eradicating persistent infection (MBC(100) = 2.5 to 5.0 microg/ml) than acute infection (MBC(100) = 10 to 50 microg/ml). The superior bactericidal effect of azithromycin against persistent infection was found to correlate with the enhanced uptake of the drug by IFN-gamma-treated infected epithelial cells. Based on these findings, we hypothesize that azithromycin should be a particularly efficacious anti-infective agent for the eradication of IFN-gamma-induced chlamydial persistent infection in vivo.
authors.affiliation: Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, 903 South 4th St., National Institutes of Health, Hamilton, MT 59840, USA.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Reveneau
authors.forename: Deborah D
authors.initials: DD
authors.lastname: Crane
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Fischer
authors.forename: Harlan D
authors.initials: HD
authors.lastname: Caldwell
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017963:Azithromycin / Q000494:pharmacology; D002690:Chlamydia Infections / Q000188:drug therapy* / Q000382:microbiology; D002692:Chlamydia trachomatis / Q000187:drug effects*; D004318:Doxycycline / Q000494:pharmacology; D004847:Epithelial Cells / Q000382:microbiology; D006367:HeLa Cells; D006801:Humans; D007371:Interferon-gamma / Q000502:physiology*; D007700:Kinetics; D046529:Microscopy, Electron, Transmission
chemical_list: D000900:Anti-Bacterial Agents; D007371:Interferon-gamma; D017963:Azithromycin; D004318:Doxycycline