1. Combination of compound screening with an animal model identifies pentamidine to prevent Chlamydia trachomatis infection.
- Author
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Knapp K, Klasinc R, Koren A, Siller M, Dingelmaier-Hovorka R, Drach M, Sanchez J, Chromy D, Kranawetter M, Grimm C, Bergthaler A, Kubicek S, Stockinger H, and Stary G
- Subjects
- Animals, Mice, Humans, Anti-Bacterial Agents pharmacology, Female, Drug Evaluation, Preclinical, Gonorrhea drug therapy, Gonorrhea microbiology, Neisseria gonorrhoeae drug effects, HeLa Cells, Chlamydia trachomatis drug effects, Chlamydia Infections drug therapy, Chlamydia Infections microbiology, Chlamydia Infections prevention & control, Pentamidine pharmacology, Disease Models, Animal
- 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., Competing Interests: Declaration of interests K.K., R.K., A.K., S.K., H.S., and G.S. are inventors on a patent application entitled “Pentamidine in the treatment of genital infections and/or STIs” (EU application number EP 24 177 796.0) filed by the Medical University of Vienna that relates to the use of pentamidine against genital infections., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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