The Emerging Pathogen Candida auris: Growth Phenotype, Virulence Factors, Activity of Antifungals, and Effect of SCY-078, a Novel Glucan Synthesis Inhibitor, on Growth Morphology and Biofilm Formation

Abstract

<i>Candida</i><i>auris</i>, a new multidrug-resistant <i>Candida</i> 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 <i>C. auris</i> 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 <i>C. auris</i> 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 <i>Candida albicans</i> (<i>P</i> = 0.01). <i>C. auris</i> 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 <i>C. auris</i> and caused complete inhibition of the growth of <i>C. auris</i> and <i>C. albicans</i> Scanning electron microscopy analysis showed that SCY-078 interrupted <i>C. auris</i> 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 (<i>P</i> < 0.05 for both comparisons). Our study shows that <i>C. auris</i> expresses several virulence determinants (albeit to a lesser extent than <i>C. albicans</i>) and is resistant to fluconazole and amphotericin B. SCY-078, the new orally bioavailable antifungal, had potent antifungal/antibiofilm activity against <i>C. auris</i>, indicating that further evaluation of this antifungal is warranted.