Murine Vaginal Co-infection with Penicillinase-ProducingNeisseria gonorrhoeaeFails to Alleviate Amoxicillin-Induced Chlamydial Persistence

Abstract

ABSTRACTChlamydia trachomatis(CT) andNeisseria gonorrhoeae(NG) cause most bacterial sexually transmitted infections (STIs) worldwide. CT/NG co-infection is more common than expected due to chance, suggesting CT/NG interaction. However, CT/NG co-infection remains largely unstudied. Obligate intracellular CT has a characteristic biphasic developmental cycle consisting of two bacterial forms, infectious elementary bodies (EBs) and non-infectious, replicating reticulate bodies (RBs), which reside within host-derived, membrane-bound intracellular inclusions. Diverse stressors cause divergence from the normal chlamydial developmental cycle to an aberrant state called chlamydial persistence. Persistence can be induced by host-specific factors such as intracellular nutrient deprivation or cytokine exposure, and exogenous factors such as beta-lactam exposure, which disrupts RB to EB conversion. Persistent chlamydiae are atypical in appearance and, as such, are called aberrant bodies (ABs), but remain viable. The primary hallmark of persistence is reversibility of this temporary non-infectious state; upon removal of the stressor, persistent chlamydiae re-enter normal development, and production of infectious EBs resumes. The beta-lactam amoxicillin (AMX) has been shown to induce chlamydial persistence in a murine vaginal infection model, using the mouse pathogenC. muridarum(CM) to model human CT infection. This remains, to date, the sole experimentally tractablein vivomodel of chlamydial persistence. Recently, we found that penicillinase-producing NG (PPNG) can alleviate AMX-induced CT and CM persistencein vitro.We hypothesized that PPNG vaginal co-infection would also alleviate AMX-induced CM persistence in mice. To evaluate this hypothesis, we modified the CM/AMX persistence mouse model, incorporating CM/PPNG co-infection. Contradicting our hypothesis, and recentin vitrofindings, PPNG vaginal co-infection failed to alleviate AMX-induced CM persistence.