Metal Nanomaterials and Hydrolytic Enzyme-Based Formulations for Improved Antifungal Activity

Abstract

Active research of metal-containing compounds and enzymes as effective antifungal agents is currently being conducted due to the growing antifungal resistance problem. Metals are attracting special attention due to the wide variety of ligands that can be used for them, including chemically synthesized and naturally obtained variants as a result of the so-called "green synthesis". The main mechanism of the antifungal action of metals is the triggering of the generation and accumulation of reactive oxygen species (ROS). Further action of ROS on various biomolecules is nonspecific. Various hydrolytic enzymes (glucanases and proteases), in turn, exhibit antifungal properties by affecting the structural elements of fungal cells (cell walls, membranes), fungal quorum sensing molecules, fungal own protective agents (mycotoxins and antibiotics), and proteins responsible for the adhesion and formation of stable, highly concentrated populations in the form of biofilms. A wide substrate range of enzymes allows the use of various mechanisms of their antifungal actions. In this review, we discuss the prospects of combining two different types of antifungal agents (metals and enzymes) against mycelial fungi and yeast cells. Special attention is paid to the possible influence of metals on the activity of the enzymes and the possible effects of proteins on the antifungal activity of metal-containing compounds.

Keywords: His6-OPH; MOFs; amyloid proteins; biofilms; chitinases; green synthesis; growth inhibition; lactamases; lactonases; mycotoxins; prionase; quorum quenching; quorum sensing.

Figure 1

Some representative metal NPs and MOFs with antifungal activities. Crystal structures of Ag (1741252), ZnO (13950), Fe₃O₄ (1612598), HKUST-1 (2091261), MIL-53-Fe (2088536), and UiO-66 (2054314) were obtained from CCDC, then expanded in Mercury (v.4.2.0, CCDC, Cambridge, UK) and visualized in PyMOL (v.1.7.6, Schrödinger Inc., New York, NY, USA). Water-accessible molecular surface is indicated by light grey while atoms are colored by element: Ag–grey, Zn–slate, O–red, Fe–orange, C–deep blue, H–white, Zr–cyan.

Figure 2

Enzymes (pink—chitinase (PDB ID: 1edq); yellow—keratinase (PDB ID: 5wsl); green—lactonase AidC (PDB ID: 4zo2); blue—peroxidase (PDB ID: 1mnp) with antifungal activities due to their catalytic action on different targets as substrates.