Aslanli Aysel, Domnin Maksim, Stepanov Nikolay, Senko Olga, Efremenko Elena
Faculty of Chemistry, Lomonosov Moscow State University, Lenin Hills 1/3, Moscow 119991, Russia.
Faculty of Chemistry, Lomonosov Moscow State University, Lenin Hills 1/3, Moscow 119991, Russia.
Int J Biol Macromol. 2024 Nov;280(Pt 4):136066. doi: 10.1016/j.ijbiomac.2024.136066. Epub 2024 Sep 27.
Recently, the lactonase activity of several enzymes (lactonase AiiA, organophosphate hydrolase (His-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 His-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, His-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.
最近，在含内酯的真菌群体感应分子（FQSM）水解过程中发现了几种酶（内酯酶AiiA、有机磷酸水解酶（His-OPH）和新德里金属β-内酰胺酶（NDM-1））的内酯酶活性。本研究旨在调查这些酶作为抗真菌组合成分与抗菌肽（AMPs）联合使用以提高其对各种真菌作用效率的可能性。为此，使用计算机模拟方法研究了各种AMPs与AiiA、NDM-1或His-OPH的相互作用，以及AMPs对这些酶在酶/AMPs组合中水解FQSM时催化特性的影响。就维持AMPs的有效性和酶的催化活性而言，选择了与3种抗菌肽杆菌肽、多粘菌素和多粘菌素B的酶组合作为最合理的组合。在体外研究了所选组合对丝状真菌和酵母细胞的抗真菌作用。发现AiiA、His-OPH和NDM-1酶与杆菌肽、多粘菌素和多粘菌素B的组合可显著提高AMPs和酶对真菌的作用效率（高达5000倍）。在与酶的多组分组合中，多粘菌素B获得了最有效的变体。
