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.