Abstract
Chlamydia trachomatis, the most common bacterial sexually transmitted disease agent worldwide, enters a viable, non-dividing and non-infectious state (historically termed persistence and more recently referred to as the chlamydial stress response) when exposed to penicillin G in culture. Notably, penicillin G-exposed chlamydiae can reenter the normal developmental cycle upon drug removal and are resistant to azithromycin-mediated killing. Because penicillin G is less frequently prescribed than other β-lactams, the clinical relevance of penicillin G-induced chlamydial persistence/stress has been questioned. The goal of this study was to determine whether more commonly used penicillins also induce C. trachomatis serovar E persistence/stress. All penicillins tested, as well as clavulanic acid, induced formation of aberrant, enlarged reticulate bodies (RB) (called aberrant bodies or AB) characteristic of persistent/stressed chlamydiae. Exposure to the penicillins and clavulanic acid also reduced chlamydial infectivity by >95%. None of the drugs tested significantly reduced chlamydial unprocessed 16S rRNA or genomic DNA accumulation, indicating that the organisms were viable, though non-infectious. Finally, recovery assays demonstrated that chlamydiae rendered essentially non-infectious by exposure to ampicillin, amoxicillin, carbenicillin, piperacillin, penicillin V, and clavulanic acid recovered infectivity after antibiotic removal. These data definitively demonstrate that several commonly used penicillins induce C. trachomatis persistence/stress at clinically relevant concentrations.
Highlights
The most common bacterial sexually transmitted disease (STD) agent in humans is Chlamydia trachomatis, with 1,412,791 reported cases in the US in 2011 (Centers for Disease Control and Prevention, 2011)
RATIONALE FOR ANTIBIOTIC-EXPOSURE CONDITIONS Though penicillin G is a characterized chlamydial persistence inducer, it is less widely used than other β-lactams
As penicillins are no longer recommended for anti-chlamydial therapy in adults, one might question the relevance of penicillin-induced chlamydial persistence in vivo
Summary
The most common bacterial sexually transmitted disease (STD) agent in humans is Chlamydia trachomatis (serovars D-K), with 1,412,791 reported cases in the US in 2011 (Centers for Disease Control and Prevention, 2011). C. trachomatis genital infection is often chronic in women, with manifestations ranging from mild infection to infertility and ectopic pregnancy (Schachter, 1999). Genital co-infections with Neisseria gonorrhoeae and C. trachomatis infections are frequent; C. trachomatis is historically the most common cause of post-gonococcal urethritis and cervicitis (PGU/PGC). Azithromycin and tetracycline/doxycycline are currently the treatments of choice for C. trachomatis infections in adults, though amoxicillin remains a recommended treatment for infected, pregnant women (Centers for Disease Control and Prevention, 2010). The infectious, extracellular form (the elementary body or EB) enters host genital epithelial cells within an endosome. After 30–70 h, the RB mature into infectious EB and are released from the infected host cell (Wyrick, 2000)
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