Enzymes Degrading Fungal Cell Wall Components vs. Those Exhibiting Lactonase Activity as Participants of Antifungals

Recently, we found that combining various antimicrobial polypeptides (AMPs) with enzymes exhibiting lactonase activity results in an antifungal agent with significantly enhanced stability and antimicrobial action efficiency. In this context, this study aims to investigate the catalytic and antifungal activity and physical-chemical properties of antifungal enzyme combinations hydrolyzing fungal cell wall components with various AMPs, comparing them with enzymes exhibiting lactonase activity (capable of hydrolyzing lactones by ring opening). Additionally, combinations of enzymes targeting the fungal cell wall and/or hydrolyzing fungal lactone-containing Quorum-sensing molecules with polyamino acids (PAAs) supplemented with fungicides (PAAF) were studied for comparison with AMP-containing combinations. Interaction models for these antifungal enzyme combinations were simulated in silico using the molecular docking method. The most promising variants, which were predicted to possess high catalytic activity, were selected, and their catalytic and physical-chemical characteristics were further evaluated in vitro. The antifungal activity of the selected combinations of enzymes with AMPs or PAAF was assessed against a number of fungi, leading to the identification of several combinations as potential candidates for inclusion in antifungals. Unexpectedly, antifungal enzyme combinations with lactonase activity were, in most cases, more effective than those with fungal-cell-wall-degrading enzymes.