Antifungal Potential of Cumin Spice Seeds, Cuminum cyminum , Against Aspergillus fumigatus : Mechanistic Insights Into Ergosterol, Melanin, and Biofilm Inhibition

Spices are aromatic culinary ingredients used worldwide for enhancing food flavors, folklore therapy, and their antiseptic, antimicrobial properties. The present study investigated the antifungal effects and underlying mechanism of supercritical‐fluid‐extracted‐oil from cumin ( Cuminum cyminum ) seeds (CcSO, hereafter) against pathogenic Aspergillus fumigatus . Listed in WHO‐Fungal Priority Pathogens List, drug‐resistant A. fumigatus infections carry high mortality rates, with limited therapeutic options. Antifungal resistance in A. fumigatus is largely attributed to genetic mutations, upregulated efflux pumps, and resilient biofilms. Chemical profiling of CcSO with GC‐MS/MS and headspace‐GC‐FID identified five major phytoconstituents, namely β‐pinene, p‐cymene, γ‐terpinene, cuminaldehyde, and 1,4‐p‐menthadien‐7‐al. At effective concentrations (0.7–1.5 mg/mL) against A. fumigatus , CcSO significantly suppressed fungal biomass and DHN‐melanin biosynthesis by downregulating the PksP gene, and reduced total ergosterol content, accompanied by the downregulation of Erg1 , Erg4 , Erg6 , and SrbA genes. Additionally, the downregulation of hyphal catalase Cat2 gene with CcSO treatment indicated the generation of oxidative stress. Aspergillus fumigatus treated with CcSO demonstrated deformed conidia, impaired hyphal growth, and delayed germination in a time‐ and dose‐dependent manner. CcSO prevented A. fumigatus biofilm formation and eradicated the pre‐formed biofilms. The current study experimentally demonstrates fungicidal activity of CsSO vapors. Notably, this vapor phase‐mediated anti‐aspergillus effect of CcSO was predominantly driven by cuminaldehyde that suppressed A. fumigatus growth without being in direct contact. Amid the global concern of antifungal resistance, combining direct (contact‐based) treatment with volatile oil therapy represents a promising natural reservoir of antifungal agents that could combat the antifungal resistance and address unmet medical needs.