Evaluating the Antibacterial and Antivirulence Activities of Floxuridine against Streptococcus suis

Streptococcus suisis an emerging zoonotic pathogen that can cause fatal diseases such as meningitis and sepsis in pigs and human beings. The overuse of antibiotics is leading to an increased level of resistance inS. suis, and novel antimicrobial agents or anti-virulence agents for the treatment of infections caused byS. suisare urgently needed. In the present study, we investigated the antibacterial activity, mode of action and anti-virulence effects of floxuridine againstS. suis. Floxuridine showed excessive antibacterial activity againstS. suisboth in vivo and in vitro; 4 × MIC of floxuridine could killS. suiswithin 8 h in a time–kill assay. Meanwhile, floxuridine disrupted the membrane structure and permeability of the cytoplasmic membrane. Molecular docking revealed that floxuridine and SLY can be directly bind to each other. Moreover, floxuridine effectively inhibited the hemolytic capacity and expression levels of the virulence-related genes ofS. suis. Collectively, these results indicate that the FDA-approved anticancer drug floxuridine is a promising agent and a potential virulence inhibitor againstS. suis.Keywords:floxuridine;Streptococcus suis;mode of action;anti-virulence