β-Tubulin of Fusarium as a Potential Target for Realization of Antifungal Activity of Ivermectin

Abstract

The analysis of the effect of ivermectin on phytopathogenic strains of Fusarium graminearum (F‑55644, F-55748) and Fusarium oxysporum f. sp. lycopersici (F-52897, F-55547) was carried out; as a result, its concentrations were established at which a fungistatic effect on the growth of colonies of the specified strains was observed (2 and 3 mg/mL). It was found that F. oxysporum strains were more susceptible in general to ivermectin than F. graminearum strains. Since it is known that ivermectin is able to interact with β-tubulin (causing a stabilization of microtubules), to explain the obtained results, a 3-dimensional model of the complex of this compound with Fusarium β-tubulin was developed and ivermectin-induced changes in the conformation of β-tubulin were determined, including, particularly, the stabilization and spiralization of the M‑loop of the β-tubulin molecule. This structural element of β-tubulin plays an important role in the lateral contacts between tubulin subunits of adjacent protofilaments within the microtubule. Since the M-loop stabilization reflects a very important feature of microtubule stabilizing agents' binding to the taxane site of β-tubulin, it can be supposed, that ivermectin possesses the same effect on Fusarium microtubules. The results obtained allow for considering ivermectin or its derivatives as potential compounds with fungicidal activity.