Veterinary session

Piglets from industrial pig farming are most susceptible to environmental pathogens during the post weaning period as a result of their weakened immune system. Streptococcus (S.) suis serves as one of these pathogens which is often treated with antimicrobial agents. The increasing occurrence of antimicrobial resistance against zoonotic bacteria such as S. suis proves the need for new therapeutical strategies, including the repositioning of drugs. In this study, susceptibilities of bacterial isolates were tested toward ten different 3-amidinophenyalanine (Phe(3-Am)) derivatives via the determination of minimum inhibitory concentration values. The protease inhibitors, such as the compounds MI-432, MI-471, and MI-476, showed remarkable antibacterial effects against S. suis. Their drug interaction potential was evaluated by using human liver microsomal cytochrome P450 (CYP450) measurements. In our work, non-tumorigenic IPEC-J2 cells and primary porcine hepatocytes were infected with S. suis for 24 h in the presence or absence of inhibitors and the putative beneficial impact of these inhibitors was investigated on cell viability (Neutral red assay), on interleukin (IL)-6 levels (ELISA technique), and on IC and EC redox status (DCFH-DA and Amplex red method). All the protease inhibitors (except MI-432) prevented S. suis-induced cell death and reduced proinflammatory IL-6 levels. It was also found that MI-432 and MI-476 had extracellular antioxidant effects in an intestinal cell model upon S. suis infection. Whereas all three inhibitors had intracellular antioxidant effects in the same model upon S. suis infection. Concentration-dependent suppression of CYP3A4 function was proven via application of all three inhibitors at concentrations 10, 25 and 50 µM to human microsomal preparations. In conclusion, our study indicates that the potential antiviral Phe(3-Am) derivatives with 2′,4′ dichloro-biphenyl moieties exert beneficial effects on IC and EC ROS status as well as IL-6 cytokine production in vitro. This suggests that these drugs are effective candidates against S. suis infection due to their antibacterial effects.