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

Abduljalil, H., Bakri, A., Albashaireh, K., Alshanta, O. A., Brown, J. L. , Sherry, L. , Kean, R., Nile, C. , McLean, W. and Ramage, G. (2022) Screening the Tocriscreen™ bioactive compound library in search for inhibitors of Candida biofilm formation. APMIS: Journal of Pathology, Microbiology and Immunology, 130(9), pp. 568-577. (doi: 10.1111/apm.13260) (PMID:35791082)

Abstract

Background and purpose: 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. Methods: To improve efficiency in antifungal drug development, we utilized a library of 1280 biologically active molecules within the Tocriscreen 2.0 Micro library. C. auris NCPF 8973 and C. 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. Results: 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. Interpretation: Together, these data provide new insights into antifungal management possibilities for Candida biofilms.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Alshanta, Ms Om Alkhir and Brown, Dr Jason and Ramage, Professor Gordon and Mclean, Professor William and Kean, Mr Ryan and Sherry, Dr Leighann and Abduljalil, Hafsa S. A. and Albashaireh, Khawlah and Nile, Dr Christopher
• Authors: Abduljalil, H., Bakri, A., Albashaireh, K., Alshanta, O. A., Brown, J. L., Sherry, L., Kean, R., Nile, C., McLean, W., and Ramage, G.
• College/School: College of Medical Veterinary and Life Sciences > School of Life Sciences; College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing > Dental School
• Journal Name: APMIS: Journal of Pathology, Microbiology and Immunology
• Publisher: Wiley
• ISSN: 0903-4641
• ISSN (Online): 1600-0463
• Published Online: 05 July 2022
• Copyright Holders: Copyright © 2022 The Authors
• First Published: First published in APMIS: Journal of Pathology, Microbiology and Immunology 130(9): 568-577
• Publisher Policy: Reproduced under a Creative Commons License