JAC Advance Access originally published online on May 26, 2004
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Journal of Antimicrobial Chemotherapy 2004 54(1):79-85; doi:10.1093/jac/dkh283
JAC vol.54 no.1 © The British Society for Antimicrobial Chemotherapy 2004; all rights reserved.
Pre-exposure of infected human endometrial epithelial cells to penicillin in vitro renders Chlamydia trachomatis refractory to azithromycin
1 Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, North Carolina; 2 Department of Microbiology, J. H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, USA
* Corresponding author. Tel: +1-423-439-6294; Fax: +1-423-439-8044; Email: pbwyrick{at}mail.etsu.edu
Objective: The clinical significance of the potential for persistent human chlamydial infections in vivo is being actively reassessed because of the increased frequency of recurrent infection with the same serovar despite compliance with an effective antibiotic regimen. The ability to extend the length of time of in vitro cultivation of polarized human endometrial epithelial cells (HEC-1B) provided the opportunity to establish a model system to determine if a persistent form of Chlamydia trachomatis had the same susceptibility as the actively growing form to a cidal concentration of azithromycin.
Methods: Polarized HEC-1B cells cultivated on extracellular matrix were infected with C. trachomatis serovar E and exposed to penicillin at 24 h post-infection (hpi) to induce a persistent infection characterized by slowly metabolizing but non-dividing, ultrastructurally aberrant reticulate bodies within the chlamydial inclusion; at 48 hpi, infected cultures were exposed to a bactericidal concentration of azithromycin for 72 h.
Results: Persistent chlamydiae were phenotypically resistant to azithromycin; the number of chlamydial inclusions on subpassage of progeny from persistent chlamydiae following removal of penicillin and recovery was essentially the same as from progeny from persistent chlamydiae following removal of penicillin and azithromycin and recovery. Neutrophils were attracted in vitro to persistently infected HEC-1B cells that had been exposed to penicillin and azithromycin.
Conclusions: Thus, this study provides evidence at the cellular microbiology level in vitro for mechanisms that could exist in vivo to create sustained, but perhaps clinically inapparent inflammation, which might eventually lead to conditions such as silent pelvic inflammatory disease.
Keywords: C. trachomatis , chlamydial persistence , polarized HEC-1B cells , pelvic inflammatory disease
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