Octyl Gallate as an Intervention Catalyst to Augment Antifungal Efficacy of Caspofungin

Abstract

Filamentous fungi such as Aspergillus spp. are opportunistic pathogens, which cause highly invasive infections, especially in immunocompromised individuals. Control of such fungal pathogens is increasingly problematic due to the small number of effective drugs available for treatment. Moreover, the increased incidence of fungal resistance to antifungal agents makes this problem a global human health issue. The cell wall integrity system of fungi is the target of antimycotic drugs echinocandins, such as caspofungin (CAS). However, echinocandins cannot completely inhibit the growth of filamentous fungal pathogens, which results in survival/escape of fungi during treatment. Chemosensitization was developed as an alternative intervention strategy, where co-application of CAS with the intervention catalyst octyl gallate (OG; chemosensitizer) greatly enhanced CAS efficacy, thus achieved ≥99.9% elimination of filamentous fungi in vitro. Based on hypersensitive responses of Aspergillus antioxidant mutants to OG, it is hypothesized that, besides destabilizing cell wall integrity, the redox-active characteristic of OG may further debilitate the fungal antioxidant system.

Antifungal Activity of Plant Waste Extracts against Phytopathogenic Fungi: Allium sativum Peels Extract as a Promising Product Targeting the Fungal Plasma Membrane and Cell Wall

“…The higher sensitivity of mutants affected in cell wall remodelling observed in this work clearly suggests that GPE targets the fungal cell wall (Figure 5). Similarly to our results, S. cerevisiae mutants affected in the cell wall integrity signalling pathway (pkc1, bck1, and slt2) have been demonstrated to be more sensitive to cell wall perturbing agents such as caspofungin, which inhibits β-(1-3)-glucan synthesis one of the main structural polysaccharides of the fungal cell wall [71,72]. Additionally, the deletion of mpkA, encoding the Aspergillus fumigatus cell wall integrity pathway homolog of the Slt2 protein of S. cerevisiae, rendered the cells more sensitive to cell wall-disturbing agents [73].…”

Molecular Docking and Comparative Inhibitory Efficacy of Naturally Occurring Compounds on Vegetative Growth and Deoxynivalenol Biosynthesis in Fusarium culmorum

“…Similarly, the ability of octyl gallate 5 as a potent antimicrobial agent was demonstrated in several studies [53][54][55]. In Aspergillus spp., besides destabilizing cell wall integrity in the target fungi, the redox-active characteristic of octyl gallate 5 may further weaken the fungal antioxidant system [55]. Magnolol 12 and honokiol 13 display antifungal, as well as antioxidant activity, against several pathogenic fungi [39,56].…”

“…The antimicrobial activity of compounds 5, 12, 13 and, to a lesser extent, of apocynin 10, has been established [39]. Similarly, the ability of octyl gallate 5 as a potent antimicrobial agent was demonstrated in several studies [53][54][55]. In Aspergillus spp., besides destabilizing cell wall integrity in the target fungi, the redox-active characteristic of octyl gallate 5 may further weaken the fungal antioxidant system [55].…”

High-efficiency fungal pathogen intervention for seed protection: new utility of long-chain alkyl gallates as heat-sensitizing agents

“…Other properties that contribute to antifungal activity of OG include nonionic surfactant action, interrupting or disorganizing the lipid bilayer-protein interface in fungal cells, and inhibition of plasma membrane H + -ATPase ( Fujita and Kubo, 2002 ). In addition, our previous work showed that OG destabilizes cell wall integrity as well as debilitates the fungal antioxidant system ( Kim et al., 2018 ). Collectively, studies indicated that OG could target multiple cellular components including cellular membranes, cell walls, AOX, antioxidant system, etc.…”