Abstract
ABSTRACTCandida auris, a new multidrug-resistant Candida spp. which is associated with invasive infection and high rates of mortality, has recently emerged. Here, we determined the virulence factors (germination, adherence, biofilm formation, phospholipase and proteinase production) of 16 C. auris isolates and their susceptibilities to 11 drugs belonging to different antifungal classes, including a novel orally bioavailable 1,3-β-d-glucan synthesis inhibitor (SCY-078). We also examined the effect of SCY-078 on the growth, ultrastructure, and biofilm-forming abilities of C. auris. Our data showed that while the tested strains did not germinate, they did produce phospholipase and proteinase in a strain-dependent manner and had a significantly reduced ability to adhere and form biofilms compared to that of Candida albicans (P = 0.01). C. auris isolates demonstrated reduced susceptibility to fluconazole and amphotericin B, while, in general, they were susceptible to the remaining drugs tested. SCY-078 had an MIC90 of 1 mg/liter against C. auris and caused complete inhibition of the growth of C. auris and C. albicans. Scanning electron microscopy analysis showed that SCY-078 interrupted C. auris cell division, with the organism forming abnormal fused fungal cells. Additionally, SCY-078 possessed potent antibiofilm activity, wherein treated biofilms demonstrated significantly reduced metabolic activity and a significantly reduced thickness compared to the untreated control (P < 0.05 for both comparisons). Our study shows that C. auris expresses several virulence determinants (albeit to a lesser extent than C. albicans) and is resistant to fluconazole and amphotericin B. SCY-078, the new orally bioavailable antifungal, had potent antifungal/antibiofilm activity against C. auris, indicating that further evaluation of this antifungal is warranted.
Highlights
Candida auris, a new multidrug-resistant Candida spp. which is associated with invasive infection and high rates of mortality, has recently emerged
We studied 16 different C. auris isolates obtained from patients in Japan, India, South Korea, and Germany and (i) characterized their morphology and virulence factors, (ii) determined their susceptibilities to 11 antifungals belonging to different antifungal classes, including a novel orally bioavailable 1,3--D-glucan synthesis inhibitor (SCY-078) with demonstrated activity against multidrug-resistant Candida spp., and (iii) evaluated the effect of SCY-078 on the growth, ultrastructure, and biofilmforming ability of C. auris [18]
In the current study, we examined 16 different C. auris isolates obtained from different parts of the world; characterized the major Candida virulence factors
Summary
A new multidrug-resistant Candida spp. which is associated with invasive infection and high rates of mortality, has recently emerged. We determined the virulence factors (germination, adherence, biofilm formation, phospholipase and proteinase production) of 16 C. auris isolates and their susceptibilities to 11 drugs belonging to different antifungal classes, including a novel orally bioavailable 1,3--D-glucan synthesis inhibitor (SCY-078). We studied 16 different C. auris isolates obtained from patients in Japan, India, South Korea, and Germany and (i) characterized their morphology and virulence factors (those that have been described for Candida species, Candida albicans, e.g., germination, adherence, biofilm formation, and phospholipase and proteinase production), (ii) determined their susceptibilities to 11 antifungals belonging to different antifungal classes, including a novel orally bioavailable 1,3--D-glucan synthesis inhibitor (SCY-078) with demonstrated activity against multidrug-resistant Candida spp., and (iii) evaluated the effect of SCY-078 on the growth, ultrastructure, and biofilmforming ability of C. auris [18]
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