In silico determination of substrate spectrum of lactonases, hydrolyzing various N-acyl homoserine lactones

Abstract

The rapid growth in the number of resistant pathogenic bacteria has led to a decrease in the effectiveness of the existing antimicrobial agents. N-acyl homoserine lactones (N-AHLs) are the key molecules responsible for the formation of antibiotic resistance of gram-negative bacteria. The combination of various lactonases, capable of hydrolyzing a wide range of N-AHLs, with antibiotics, is one of the most appropriate ways to solve the problem of maintaining the effectiveness of the latter. The most interesting is the combination of lactonases with different substrate spectrum of action. In this study, using the molecular docking method, we investigated the substrate range of various lactonases in order to select enzymes suitable to combine with hexahistidine-tagged organophosphorus hydrolase (His6-OPH), for which high lactonase activity against a number of N-AHLs and the possibility of complex formation with antibiotics have been shown previously. It was found that all the studied lactonases hydrolyze predominantly long chain N-AHLs, while, among all studied lactonases, the SsoPox enzyme from the class of phosphotriesterases-like lactonases was the best candidate for the development of combined enzyme preparations.