Investigation of the effect of sanguinarine and ascorbic acid combinations against ica-dependent biofilm producing staphylococcus aureus isolates

The prevalence of Staphylococcus aureus (S. aureus), which causes nosocomial and community-acquired infections, has increased in recent years. The treatment of S. aureus which causes biofilm-associated infections are difficult. In this study, it was aimed to create more effective treatment options with lower doses of agents by using combination treatments of agents having distinct action mechanisms against biofilm-producer S. aureus. In our study, after the presences of icaA, icaD, blaZ, blaI, blaRI and atl genes in biofilm producer methicillin sensitive S. aureus (MSSA) isolates were detected, MICs and MBCs of sanguinarine and ascorbic acid against isolates were determined. Antibacterial and antibiofilm activities of sanguinarine and ascorbic acid combinations containing 8 different doses of agents, starting from 8 fold of MIC to 16 fold of sub-MIC against planktonic S. aureus clinical isolates were investigated by checkerboard and MtP methods, respectively. In addition, the effects of sole and in combinations of agents containing 16 sub-MIC were investigated against sessile S. aureus by MBEC method. The effects of sole and combined treatments of 1/4 MIC sanguinarine and ascorbic acid against expression levels of icaA, icaD and atl genes of sessile S. aureus isolates were observed after 12 hours of incubation. When the sole and combined effects of sanguinarine and ascorbic acid against planktonic isolates were examined, the FIC indexes of MSSA1, MSSA2, MSSA3 and MSSA4 isolates were found to be 0.745, 0.745, 0.920, 0.699, respectively, with partial synergistic effects. It was observed that agent combinations reduce biofilm formation and mature biofilms. It was also observed that the reductions in icaA, icaD and atl gene expression levels of MSSA isolates. According to the results of the study, sanguinarine and ascorbic acid combinations may be an alternative treatment option in ica-dependent biofilm-producer S. aureus infections. Keywords: S. aureus, Ica-dependent biofilm, Sanguinarine, Ascorbic Acid, Synergism.