A large screen identifies beta-lactam antibiotics which can be repurposed to target the syphilis agent

Syphilis, caused by Treponema pallidum subsp. pallidum, is re-emerging globally. Benzathine penicillin G is the preferred treatment, but supply shortages, allergy concerns, and potential for resistance underscore the need for alternative therapeutics. Leveraging recent advances in continuous in vitro cultivation of T. pallidum, the authors conducted a high-throughput screen of nearly 100 β-lactam antibiotics. Using molecular and cellular assays, several β-lactams were identified that matched or outperformed benzathine penicillin G in vitro. These candidates include approved antibiotics and synthetic derivatives. The study provides both potential therapeutic options for syphilis and technical approaches to investigate T. pallidum biology.