Abstract
An urgent need exists for new antifungal compounds to treat fungal infections in immunocompromised patients. The aim of the current study was to investigate the potency of a novel antifungal compound, MYC-053, against the emerging yeast and yeast-like pathogens Candida glabrata, Candida auris, Cryptococcus neoformans, and Pneumocystis species. MYC-053 was equally effective against the susceptible control strains, clinical isolates, and resistant strains, with MICs of 0.125 to 4.0 μg/ml. Notably, unlike other antifungals such as azoles, polyenes, and echinocandins, MYC-053 was effective against Pneumocystis isolates, therefore being the only synthetic antifungal that may potentially be used against Pneumocystis spp., Candida spp., and Cryptococcus spp. MYC-053 was highly effective against preformed 48-h-old C. glabrata and C. neoformans biofilms, with minimal biofilm eradication concentrations equal to 1 to 4 times the MIC. Together, these data indicated that MYC-053 may be developed into a promising antifungal agent for the treatment and prevention of invasive fungal infections caused by yeasts and yeast-like fungi.
Highlights
An urgent need exists for new antifungal compounds to treat fungal infections in immunocompromised patients
We describe the fungicidal activity of a novel antifungal compound, MYC-053 {sodium 5-[1-(3,5-dichloro-2-hydroxyphenyl)methylideneamino]-6-methyl1,2,3,4-tetrahydro-2,4-pyrimidinedionate} (Fig. 1), which is not related to any existing classes of antifungal agents and was investigated against planktonic and biofilmforming Candida spp., Cryptococcus spp., and Pneumocystis spp. [27,28,29,30,31]
In the current study, we described a novel antifungal drug candidate, MYC-053, which exhibited a high level of antimicrobial activity against C. glabrata, C. auris, C. neoformans, and Pneumocystis spp. in vitro that are well-known causes of morbidity in immunocompromised patients, being characterized by growing antibiotic resistance [35,36,37,38,39,40,41,42]
Summary
An urgent need exists for new antifungal compounds to treat fungal infections in immunocompromised patients. MYC-053 was highly effective against preformed 48-h-old C. glabrata and C. neoformans biofilms, with minimal biofilm eradication concentrations equal to 1 to 4 times the MIC. Together, these data indicated that MYC-053 may be developed into a promising antifungal agent for the treatment and prevention of invasive fungal infections caused by yeasts and yeast-like fungi. Resistance to echinocandins is increasing among C. glabrata isolates, with reported resistance rates of 3% to 12% in different countries [14, 15] Another global health care concern is the emerging multidrug-resistant pathogenic species Candida auris [16, 17]. The drug resistance rate of C. auris exceeds that of C. glabrata, with over 41% of isolates reportedly resistant to at least two antifungal classes [18]
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