Antimicrobial peptide-antibiotic synergy exerts anti-streptococcus suis infection by membrane disruption, ROS induction and biofilm inhibition

With the increasing emergence of antimicrobial resistance, the rise of multidrug-resistant Streptococcus suis ( S. suis ) has caused a great threat on global public health. The combination of antimicrobial peptide (AMP) and antibiotics is an efficient strategy to enhance antibacterial efficacy and combat bacterial antibiotic resistance. In this study, the antibacterial efficacy of chicken-derived AMP CATH-1 combined with tetracycline against S. suis infection was investigated in vitro and in vivo . The results showed that combination of CATH-1 and tetracycline exerted effectively anti- S. suis activity, which rapidly killed all tested bacteria in 60 min. In the mice infection model, CATH-1 combined with tetracycline improved survival rate of SC19-infected mice, reduced bacterial load in different tissues and alleviated the inflammatory response as well as inflammatory damage. Furthermore, CATH-1 reduced the emergence of bacterial resistance to tetracycline. Mechanically, CATH-1 disrupted cell membrane via SEM observation and SYTO9/PI staining. CATH-1 in combination with tetracycline aggravated reactive oxygen species (ROS) accumulation and proton motive force (PMF) disruption compared to CATH-1 or tetracycline alone. In addition, CATH-1 inhibited efflux pump function. Importantly, we identified a critical gene steAB associated with biofilm formation and CATH-1 alone or in combination with tetracycline inhibited biofilm formation. Our study shows effective anti- S. suis infection of CATH-1-tetracycline synergy, which provides the basis on the development of AMP as additives to antibiotics.