Combination of compound screening with an animal model identifies pentamidine to prevent Chlamydia trachomatis infection

Chlamydia trachomatis (Ct) is the most common cause for bacterial sexually transmitted infections (STIs) worldwide with a tremendous impact on public health. With the aim to unravel novel targets of the chlamydia life cycle, we screen a compound library and identify 28 agents to significantly reduce Ct growth. The known anti-infective agent pentamidine—one of the top candidates of the screen—shows anti-chlamydia activity in low concentrations by changing the metabolism of host cells impairing chlamydia growth. Furthermore, it effectively decreases the Ct burden upon local or systemic application in mice. Pentamidine also inhibits the growth of Neisseria gonorrhea (Ng), which is a common co-infection of Ct. The conducted compound screen is powerful in exploring antimicrobial compounds against Ct in a medium-throughput format. Following thorough in vitro and in vivo assessments, pentamidine emerges as a promising agent for topical prophylaxis or treatment against Ct and possibly other bacterial STIs. [Display omitted] •A compound screen identifies 28 non-antibiotics inhibiting Chlamydia trachomatis•Pentamidine inhibits chlamydia replication indirectly via the host cells•Systemic and intrauterine pentamidine treatment decreases chlamydia burden in mice•Pentamidine is a promising candidate for prophylaxis against bacterial STIs As the numbers of sexually transmitted infections are rising, innovative prophylactic measures are needed. Knapp et al. performed a medium-throughput compound screen to identify new drugs inhibiting Chlamydia trachomatis growth in cell lines. The top hits were tested in a Chlamydia trachomatis mouse model for their ability to prevent infection.