Orlistat impairs Chlamydia trachomatis development by disrupting its developmental cycle

Chlamydia trachomatis is a common sexually transmitted bacterial pathogen that often causes urogenital infection and may progress to chronic inflammation and fibrosis due to its clinically silent nature. Although azithromycin and doxycycline are widely used for treatment, therapeutic failure has been documented in clinical cases. In this study, we demonstrate that orlistat disrupts the chlamydial developmental cycle both in vitro and in vivo. Orlistat inhibits early stages of chlamydial infection, reticulate body replication, and reticulate body-to-elementary body differentiation. Transcriptomic analysis revealed significant downregulation of multiple genes associated with mid-to-late developmental stages, indicating disruption of the chlamydial developmental program. These findings suggest that orlistat interferes with chlamydial growth and development, although the underlying mechanisms have not been fully defined.