Of the different plant defense compounds, phytoanticipins and phytoalexins have been widely characterized over several decades. Plants produce a large number of chemicals, some of which are used as primary metabolites, while others are used to protect themselves from pathogens and herbivores. In addition, given that antifungal agents such as azole drugs, polyene drugs, and flucytosine have adverse effects, there is an urgent need for the identification of novel compounds and targets for treatment of this condition, for the betterment of public health.
Despite global concerns, therapeutic options are limited due to the evolutionarily similar cellular structures observed in both humans and fungi. Recently, it has been estimated that there are more than 4,000,000 infections caused by opportunistic fungal pathogens annually.
The incidence rate of systemic and invasive mycoses caused by opportunistic fungal pathogens, including Candida albicans, Aspergillus fumigatus, and Cryptococcus neoformans, has increased over the past decades due to the extension of human lifespan and increase in the number of immunocompromised patients with organ transplantation. Collectively, this study sheds light on the antifungal mechanisms of thymol against C. Furthermore, thymol treatment reduced endogenous ergosterol content by decreasing the expression of ergosterol biosynthesis genes in a HOG MAPK pathway-dependent manner. We demonstrated that thymol decreased N-glycosylation by regulating the expression levels of genes involved in glycan-mediated post-translational modifications. Thymol treatment reduced the intracellular concentration of Ca 2+ by controlling the expression levels of calcium transporter genes in a calcineurin-dependent manner. Using a reverse genetics approach, the present study revealed that thymol, a monoterpene alcohol from Thymus vulgaris L., (Lamiaceae), exhibits antifungal activity against Cryptococcus neoformans by regulating multiple signaling pathways including calcineurin, unfolded protein response, and HOG (high-osmolarity glycerol) MAPK (mitogen-activated protein kinase) pathways. Although plants produce a diversity of chemicals to protect themselves from pathogens, the molecular targets and modes of action of these plant-derived chemicals have not been well characterized. Despite increasing attention, limited options are available for the treatment of systematic and invasive mycoses, owing to the evolutionary similarity between humans and fungi. Due to lifespan extension and changes in global climate, the increase in mycoses caused by primary and opportunistic fungal pathogens is now a global concern.