Action enhancement of antimicrobial peptides by their combination with enzymes hydrolyzing fungal quorum molecules

Recently, the lactonase activity of several enzymes (lactonase AiiA, organophosphate hydrolase (His6-OPH) and New Delhi metallo-β-lactamase (NDM-1)) was revealed in the hydrolysis of lactone-containing fungal Quorum Sensing molecules (FQSM). This study was aimed at the investigation of possible use of these enzymes as components of antifungal combinations with antimicrobial peptides (AMPs) to increase their action efficiency against various fungi. For this, the interaction of various AMPs with AiiA, NDM-1 or His6-OPH, as well as the effect of AMPs on the catalytic characteristics of these enzymes in the hydrolysis of FQSM in enzyme/AMP combinations, were studied using in silico computer modeling methods. Enzymes combinations with 3 AMPs Bacitracin, Colistin and Polymyxin B were selected as the most rational in terms of maintaining the effectiveness of AMP and the catalytic activity of enzymes. The antifungal action of the selected combinations against cells of mycelial fungi and yeast was studied in vitro. It was found that combinations of the enzymes AiiA, His6-OPH and NDM-1 with Bacitracin, Colistin and Polymyxin B provide a significant increase in the action efficiency (up to 5000 times) of both AMPs and enzymes against fungi. The most effective variants were obtained for Polymyxin B in multicomponent combinations with enzymes. [Display omitted] •Lactonases were combined with bacitracin, polymyxin B and colistin in silico.•The antifungal activity of selected combinations was determined in vitro.•The individual efficiency of antimicrobials and enzymes increases in combinations.•The most effective combinations of lactonases were obtained with polymyxin B.•Combinations with several enzymes showed the most promising results against yeasts.