Abstract
Fungal infections affect 300 million people and cause 1.5 million deaths globally per year. With the number of immunosuppressed patients increasing steadily, there is an increasing number of patients infected with opportunistic fungal infections such as infections caused by the species of Candida and Cryptococcus. In fact, the drug-resistant Can. krusei and the emerging pan-antifungal resistant Can. auris pose a serious threat to human health as the existing limited antifungals are futile. To further complicate therapy, fungi produce capsules and spores that are resistant to most antifungal drugs/host defenses. Novel antifungal drugs are urgently needed to fill unmet medical needs. From screening a collection of medicinal plant sources for antifungal activity, we have identified an active fraction from the rhizome of Cyperus rotundus, the nut grass plant. The fraction contained α-Cyperone, an essential oil that showed fungicidal activity against different species of Candida. Interestingly, the minimal inhibitory concentration of α-Cyperone was reduced 8-fold when combined with a clinical antifungal drug, fluconazole, indicating its antifungal synergistic potential and could be useful for combination therapy. Furthermore, α-Cyperone affected the synthesis of the capsule in Cryp. neoformans, a causative agent of fungal meningitis in humans. Further work on mechanistic understanding of α-Cyperone against fungal virulence could help develop a novel antifungal agent for drug-resistant fungal pathogens.
Highlights
Fungal diseases contribute to significant morbidity and mortality in humans
It is estimated that nearly a billion people are infected with mucosal or superficial fungal diseases and 150 million people are affected with invasive fungal diseases [1]
Humans are a natural reservoir for C. albicans, which colonizes on the mucosal surfaces and can disseminate systemically by their yeast-tohypha conversion, leading to life-threatening invasive fungal infections
Summary
Fungal diseases contribute to significant morbidity and mortality in humans. It is estimated that nearly a billion people are infected with mucosal or superficial fungal diseases and 150 million people are affected with invasive fungal diseases [1]. The major invasive fungal infections include candidiasis, aspergillosis, cryptococcal meningitis, pneumocystis pneumonia, and histoplasmosis, which are responsible for over 1.6 million deaths globally [1]. Among the various fungal pathogens that affect humans, Candida albicans is the major fungus that is frequently associated with Candidiasis, causing a mortality rate up to 50% [2,3]. Humans are a natural reservoir for C. albicans, which colonizes on the mucosal surfaces (oral, GI, and urogenital tracts) and can disseminate systemically by their yeast-tohypha conversion, leading to life-threatening invasive fungal infections. An emerging Candida fungal pathogen, C. auris, is a major concern due to its pan-antifungal resistance, persistence in hospital environments as well as its invasive virulence potential with a high mortality rate (60%) [5,6]
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