title: 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: Candidaauris, a new multidrug-resistantCandidaspp. 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 16C. aurisisolates 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 ofC. aurisOur 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 ofCandida albicans(P= 0.01).C. aurisisolates demonstrated reduced susceptibility to fluconazole and amphotericin B, while, in general, they were susceptible to the remaining drugs tested. SCY-078 had an MIC90of 1 mg/liter againstC. aurisand caused complete inhibition of the growth ofC. aurisandC. albicansScanning electron microscopy analysis showed that SCY-078 interruptedC. auriscell 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 thatC. aurisexpresses several virulence determinants (albeit to a lesser extent thanC. albicans) and is resistant to fluconazole and amphotericin B. SCY-078, the new orally bioavailable antifungal, had potent antifungal/antibiofilm activity againstC. auris, indicating that further evaluation of this antifungal is warranted.
authors.affiliation: Center for Medical Mycology, Case Western Reserve University, and University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA.
authors.forename: Emily
authors.initials: E
authors.lastname: Larkin
authors.affiliation: Center for Medical Mycology, Case Western Reserve University, and University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Hager
authors.affiliation: Center for Medical Mycology, Case Western Reserve University, and University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA.
authors.forename: Jyotsna
authors.initials: J
authors.lastname: Chandra
authors.affiliation: Center for Medical Mycology, Case Western Reserve University, and University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA.
authors.forename: Pranab K
authors.initials: PK
authors.lastname: Mukherjee
authors.affiliation: Center for Medical Mycology, Case Western Reserve University, and University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Retuerto
authors.affiliation: Center for Medical Mycology, Case Western Reserve University, and University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA.
authors.forename: Iman
authors.initials: I
authors.lastname: Salem
authors.affiliation: Center for Medical Mycology, Case Western Reserve University, and University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Long
authors.affiliation: Center for Medical Mycology, Case Western Reserve University, and University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA.
authors.forename: Nancy
authors.initials: N
authors.lastname: Isham
authors.affiliation: Astellas Pharma Global Development, Inc., Northbrook, Illinois, USA.
authors.forename: Laura
authors.identifier: 0000-0002-4493-4652
authors.initials: L
authors.lastname: Kovanda
authors.affiliation: Scynexis Inc., Jersey City, New Jersey, USA.
authors.forename: Katyna
authors.initials: K
authors.lastname: Borroto-Esoda
authors.affiliation: Scynexis Inc., Jersey City, New Jersey, USA.
authors.forename: Steve
authors.initials: S
authors.lastname: Wring
authors.affiliation: Scynexis Inc., Jersey City, New Jersey, USA.
authors.forename: David
authors.initials: D
authors.lastname: Angulo
authors.affiliation: Center for Medical Mycology, Case Western Reserve University, and University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA Mahmoud.Ghannoum@Case.edu.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Ghannoum
mesh_terms: D000666:Amphotericin B / Q000494:pharmacology; D000935:Antifungal Agents / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development; D002175:Candida / Q000187:drug effects* / Q000254:growth & development / Q000302:isolation & purification / Q000472:pathogenicity*; D002176:Candida albicans / Q000254:growth & development / Q000472:pathogenicity; D002177:Candidiasis / Q000188:drug therapy / Q000382:microbiology; D002448:Cell Adhesion; D002455:Cell Division / Q000187:drug effects; D026141:Drug Resistance, Multiple, Fungal; D015725:Fluconazole / Q000494:pharmacology; D005936:Glucans / Q000096:biosynthesis; D006027:Glycosides / Q000494:pharmacology*; D006801:Humans; D008826:Microbial Sensitivity Tests; D010447:Peptide Hydrolases / Q000096:biosynthesis; D010740:Phospholipases / Q000096:biosynthesis; D014315:Triterpenes / Q000494:pharmacology*; D037521:Virulence Factors
chemical_list: D000935:Antifungal Agents; D005936:Glucans; D006027:Glycosides; D014315:Triterpenes; D037521:Virulence Factors; D000666:Amphotericin B; D015725:Fluconazole; C569338:ibrexafungerp; D010740:Phospholipases; D010447:Peptide Hydrolases
keywords: Candida auris; SCY-078; biofilm; virulence