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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
Open accessAbstract
Candida 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 MIC 90 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.
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“Regarding its anti-biofilm activity, somewhat unsurprisingly since it shares the same target with echinocandins, ibrexafungerp has been shown to display activity against biofilms formed by different Candida species, including C. albicans, C. parapsilosis, C. tropicalis, C. glabrata [44], and most recently C. auris [45].”
From Antifungal therapy of Candida biofilms: Past, present and future (2023) · cites this paper as [45]
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“Importantly, SCY-078 appears to be active against echinocandin-resistant and azole-resistant Candida strains, including C. auris [111,112,113].”
From Treatment of Invasive Candidiasis: A Narrative Review (2018) · cites this paper as [112]
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“However, exposure to various cues that induce C. albicans filamentation does not induce morphogenesis in C. auris, suggesting divergence in the circuitry governing the yeast-to-filament transition between the two Candida species (23).”
From Genetic Analysis of Candida auris Implicates Hsp90 in Morphogenesis and Azole Tolerance and Cdr1 in Azole Resistance (2019) · cites this paper as [23]
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Metadata
- Authors
- Larkin, E., Hager, C., Chandra, J., Mukherjee, P. K., Retuerto, M., Salem, I., Long, L., Isham, N., Kovanda, L., Borroto-Esoda, K., Wring, S., Angulo, D., & Ghannoum, M.
- Affiliations
- University Hospitals of Cleveland (US)
- Astellas Pharma (United States) (US)
- Scynexis Inc., Jersey City, New Jersey, USA
- Scynexis (United States) (US)
- Corresponding author
- Ghannoum, Mahmoud
- ORCID
- Venue
- Antimicrobial Agents and Chemotherapy
- Publisher
- American Society for Microbiology
- Published
- 2017-05
- Volume
- 61
- Issue
- 5
- ISSN
- 0066-4804 (ISSN-L)
- 1098-6596
- PMC
- PMC5404565
- OpenAlex
- W2589939125
- Cited by
- 395
- References
- 53
- Citations by year
- 2026: 24 · 2025: 25 · 2024: 31 · 2023: 36 · 2022: 30 · 2021: 49 · 2020: 67 · 2019: 51 · 2018: 42 · 2017: 39
- FWCI
- 42.10
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Antimicrobial Agents and Chemotherapy (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Case Western Reserve University
- National Institutes of Health
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (P30AR039750)
- National Institute of Dental and Craniofacial Research (R01DE024228)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Health Sciences › Medicine › Infectious Diseases › Fungal Infections and Studies
- Keywords
- Candida auris, antifungal susceptibility, fluconazole resistance, amphotericin B resistance, biofilm formation, antibiofilm activity, fungal virulence factors, phospholipase, proteolytic enzymes, fungal adhesion, cell division inhibition, Candida albicans comparison, multidrug-resistant fungi
- MeSH terms
- Amphotericin B, Antifungal Agents, Candida, Candida albicans, Candidiasis, Cell Adhesion, Cell Division, Glucans, Glycosides, Humans, Microbial Sensitivity Tests, Peptide Hydrolases, Phospholipases, Triterpenes, Fluconazole, Biofilms, Drug Resistance, Multiple, Fungal, Virulence Factors
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