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

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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.

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Funding

This study was carried out within the budget theme (code # 6541230) and was financially supported by the National Academy of Sciences of Ukraine.

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Authors and Affiliations

  1. Institute of Food Biotechnology and Genomics, National Academy of Sciences of Ukraine, 04123, Kyiv, Ukraine

    Y. O. Kustovskiy, A. Y. Buziashvili, S. P. Ozheredov, Y. B. Blume & A. I. Yemets

  2. National University of Kyiv–Mohyla Academy, 04070, Kyiv, Ukraine

    Y. O. Kustovskiy & A. I. Yemets

Authors
  1. Y. O. Kustovskiy
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  2. A. Y. Buziashvili
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  3. S. P. Ozheredov
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  4. Y. B. Blume
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  5. A. I. Yemets
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Correspondence to Y. O. Kustovskiy or A. I. Yemets.

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Kustovskiy, Y.O., Buziashvili, A.Y., Ozheredov, S.P. et al. β-Tubulin of Fusarium as a Potential Target for Realization of Antifungal Activity of Ivermectin. Cytol. Genet. 58, 1–10 (2024). https://doi.org/10.3103/S009545272401002X

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