Screening the Tocriscreen™ bioactive compound library in search for inhibitors of Candida biofilm formation

Hafsa Abduljalil, Ahmed Bakri, Khawlah Albashaireh, Om Alkhir Alshanta, Jason L. Brown, Leighann Sherry, Ryan Kean, Christopher Nile, William McLean, Gordon Ramage

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)
6 Downloads (Pure)

Abstract

Biofilms formed by Candida species present a significant clinical problem due to the ineffectiveness of many conventional antifungal agents, in particular the azole class. We urgently require new and clinically approved antifungal agents quickly for treatment of critically ill patients. To improve efficiency in antifungal drug development, we utilized a library of 1280 biologically active molecules within the Tocriscreen 2.0 Micro library. Candida auris NCPF 8973 and Candida albicans SC5314 were initially screened for biofilm inhibitory activity using metabolic and biomass quantitative assessment methods, followed up by targeted evaluation of five selected hits. The initial screening (80% metabolic inhibition rate) revealed that there was 90 and 87 hits (approx. 7%) for C. albicans and C. auris, respectively. Additionally, all five compounds selected from the initial hits exhibited a biofilm inhibition effect against several key Candida species tested, including C. glabrata and C. krusei. Toyocamycin displayed the most potent activity at concentrations as low as 0.5 μg/mL, though was limited to inhibition. Darapladib demonstrated an efficacy for biofilm inhibition and treatment at a concentration range from 8 to 32 μg/mL and from 16 to 256 μg/mL, respectively. Combinational testing with conventional antifungals against C. albicans strains demonstrated a range of synergies for planktonic cells, and notably an anti-biofilm synergy for darapladib and caspofungin. Together, these data provide new insights into antifungal management possibilities for Candida biofilms.
Original languageEnglish
Pages (from-to)568-577
Number of pages10
JournalAPMIS
Volume130
Issue number9
Early online date20 Jul 2022
DOIs
Publication statusPublished - 3 Aug 2022

Keywords

  • Biofilm
  • Candida auris
  • Candida albicans
  • drug repurposing

ASJC Scopus subject areas

  • Microbiology (medical)
  • Pathology and Forensic Medicine
  • Immunology and Allergy

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