Faculty of Chemistry, Lomonosov Moscow State University, Lenin Hills 1/3, Moscow 119991, Russia.
Biomolecules. 2024 Mar 21;14(3):383. doi: 10.3390/biom14030383.
Since the growing number of fungi resistant to the fungicides used is becoming a serious threat to human health, animals, and crops, there is a need to find other effective approaches in the eco-friendly suppression of fungal growth. One of the main mechanisms of the development of resistance in fungi, as well as in bacteria, to antimicrobial agents is quorum sensing (QS), in which various lactone-containing compounds participate as signaling molecules. This work aimed to study the effectiveness of action of enzymes exhibiting lactonase activity against fungal signaling molecules. For this, the molecular docking method was used to estimate the interactions between these enzymes and different lactone-containing QS molecules of fungi. The catalytic characteristics of enzymes such as lactonase AiiA, metallo-β-lactamase NDM-1, and organophosphate hydrolase His-OPH, selected for wet experiments based on the results of computational modeling, were investigated. QS lactone-containing molecules (butyrolactone I and γ-heptalactone) were involved in the experiments as substrates. Further, the antifungal activity of the enzymes was evaluated against various fungal and yeast cells using bioluminescent ATP-metry. The efficient hydrolysis of γ-heptalactone by all three enzymes and butyrolactone I by His-OPH was demonstrated for the first time. The high antifungal efficacy of action of AiiA and NDM-1 against most of the tested fungal cells was revealed.
由于抗真菌剂的真菌耐药性日益增加，对人类健康、动物和农作物构成严重威胁，因此需要寻找其他有效的生态友好型方法来抑制真菌生长。真菌和细菌对抗生素产生耐药性的主要机制之一是群体感应（QS），其中各种含有内酯的化合物作为信号分子参与其中。这项工作旨在研究具有内酯酶活性的酶对真菌信号分子的作用效果。为此，使用分子对接方法来估计这些酶与真菌不同的含有内酯的 QS 分子之间的相互作用。根据计算建模的结果，选择了 AiiA 乳糖酶、金属β-内酰胺酶 NDM-1 和有机磷水解酶 His-OPH 等酶进行湿实验，并研究了它们的催化特性。实验中使用了含有 QS 内酯的分子（丁内酯 I 和γ-庚内酯）作为底物。此外，使用生物发光 ATP 测定法评估了这些酶对各种真菌和酵母细胞的抗真菌活性。这是首次证明了三种酶都能有效地水解γ-庚内酯，而 His-OPH 能有效地水解丁内酯 I。AiiA 和 NDM-1 对大多数测试真菌细胞的高效抗真菌作用效果也被揭示出来。
