LAUSR

AIM Antimicrobial resistance (AMR) has become a global concern. Developing novel antimicrobials is one of the most effective approaches in tackling AMR. Considering its relatively low cost and risk, drug repurposing has been proposed as a valuable approach for novel antimicrobial discovery. The aim of this study was to screen for antimicrobial compounds against Streptococcus suis, an important zoonotic bacterial pathogen, from an FDA-approved drug library. METHODS AND RESULTS In this study, we tested the antimicrobial activity of 1815 FDA-approved drugs against S. suis. 67 hits were obtained that showed a growth inhibition of more than 98%. After excluding already known antibiotics and antiseptics, twelve compounds were subjected to minimal inhibition concentration (MIC) assessment against S. suis. This showed that pralatrexate, daunorubicin (hydrochloride), teniposide, aclacinomycin A hydrochloride, and floxuridine gave a relatively low MIC, ranging from 0.85 to 5.25 μg/mL. Apart from pralatrexate, the remaining four drugs could also inhibit the growth of antimicrobial-resistant S. suis. It was also demonstrated that these four drugs had better efficacy against Gram-positive bacteria than Gram-negative bacteria. Cytotoxicity assays showed that floxuridine and teniposide had a relatively high 50% cytotoxic concentration (CC50 ). The in vivo efficacy of floxuridine was analyzed using a Galleria mellonella larvae infection model, and the results showed that floxuridine was effective in treating S. suis infection in vivo. CONCLUSIONS Five compounds from the FDA-approved drug library showed high antimicrobial activity against S. suis, among which floxuridine displayed potent in vivo efficacy that is worth further development. SIGNIFICANCE AND IMPACT OF STUDY Our study identified several antimicrobial compounds that are effective against S. suis, which provides a valuable starting point for further antimicrobial development.