Abstract
ABSTRACTThere is a rising global incidence of Candida strains with high levels of resistance to fluconazole and other antifungal drugs, hence the need for novel antifungal treatment strategies. Here, we describe the first evidence of antifungal activity of Q-Griffithsin (Q-GRFT), a recombinant oxidation-resistant variant of Griffithsin, a marine red algal lectin with broad-spectrum antiviral activity. We demonstrated that Q-GRFT binds to α-mannan in the Candida albicans cell wall. We also observed that Q-GRFT binding disrupted cell wall integrity and induced reactive oxidative species (ROS) formation, resulting in cell death. Furthermore, we showed that Q-GRFT inhibited the growth of other Candida species C. glabrata, C. parapsilosis, and C. krusei and had modest activity against some strains of multi- and pandrug-resistant C. auris. We found that Q-GRFT induced differential expression of numerous genes involved in response to cell stress, including those responsible for neutralizing ROS production and cell cycle regulation. In conclusion, this novel antifungal activity suggests that Q-GRFT is potentially an ideal drug candidate and represents an alternative strategy for the prevention and treatment of candidiasis.IMPORTANCE Fungal infections contribute to morbidity and mortality annually, and the number of organisms that are nonresponsive to the current available drug regimens are on the rise. There is a need to develop new agents to counter these infections and to add to the limited arsenal available to treat fungal infections. Our study has identified Q-GRFT, a broad-spectrum antiviral protein that harbors growth-inhibitory activity against several Candida strains, as a potential candidate for the prevention and treatment of fungal infections.
Highlights
There is a rising global incidence of Candida strains with high levels of resistance to fluconazole and other antifungal drugs, the need for novel antifungal treatment strategies
We investigated the effect of Q-GRFT on the growth of representative bacteria found in the human gut, including Lactobacillus acidophilus, Lactobacillus casei, Escherichia coli strain K-12, Antifungal Activity of Q-Griffithsin
The selected bacterial components were incubated in the presence of various concentrations of Q-GRFT in broth media, and growth was established by determining optical density (OD) measurements over time using a plate reader
Summary
There is a rising global incidence of Candida strains with high levels of resistance to fluconazole and other antifungal drugs, the need for novel antifungal treatment strategies. In particular there are increasing reports of Candida species that demonstrate high resistance to fluconazole and other antifungal drugs [3] This problem is further complicated by the narrow spectrum and limited arsenal of currently available options, which include only polyenes, azoles, echinocandins, and flucytosine for invasive infections and allylamines for dermal mycoses [4,5,6,7]. These current agents have been associated with toxicity and drug interactions, subsequently limiting their utility and contributing to the high morbidity and mortality in fungal infections [8, 9]. The difficulty in managing the treatment of patients with multidrug-resistant Candida species and pandrug-resistant isolates of Candida auris in the United States and globally [27,28,29] underscores the urgent need to develop new antifungal agents and therapeutic strategies
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