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

化合物筛选结合动物模型,发现喷他脒可预防沙眼衣原体感染。

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作者:Katja Knapp ,Romana Klasinc ,Anna Koren ,Magdalena Siller ,Ruth Dingelmaier-Hovorka ,Mathias Drach ,Juan Sanchez ,David Chromy ,Marlene Kranawetter ,Christoph Grimm ,Andreas Bergthaler ,Stefan Kubicek ,Hannes Stockinger ,Georg Stary

Abstract

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.

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