A Screen for Small Molecules to Target <i>Candida albicans</i> Biofilms
The human fungal pathogen <i>Candida albicans</i> can form biofilms on biotic and abiotic surfaces, which are inherently resistant to antifungal drugs. We screened the Chembridge Small Molecule Diversity library containing 30,000 “drug-like” small molecules and identified 45 compounds th...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-12-01
|
| Series: | Journal of Fungi |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2309-608X/7/1/9 |
| _version_ | 1797543393352482816 |
|---|---|
| author | Matthew B. Lohse Craig L. Ennis Nairi Hartooni Alexander D. Johnson Clarissa J. Nobile |
| author_facet | Matthew B. Lohse Craig L. Ennis Nairi Hartooni Alexander D. Johnson Clarissa J. Nobile |
| author_sort | Matthew B. Lohse |
| collection | DOAJ |
| description | The human fungal pathogen <i>Candida albicans</i> can form biofilms on biotic and abiotic surfaces, which are inherently resistant to antifungal drugs. We screened the Chembridge Small Molecule Diversity library containing 30,000 “drug-like” small molecules and identified 45 compounds that inhibited biofilm formation. These 45 compounds were then tested for their abilities to disrupt mature biofilms and for combinatorial interactions with fluconazole, amphotericin B, and caspofungin, the three antifungal drugs most commonly prescribed to treat <i>Candida</i> infections. In the end, we identified one compound that moderately disrupted biofilm formation on its own and four compounds that moderately inhibited biofilm formation and/or moderately disrupted mature biofilms only in combination with either caspofungin or fluconazole. No combinatorial interactions were observed between the compounds and amphotericin B. As members of a diversity library, the identified compounds contain “drug-like” chemical backbones, thus even seemingly “weak hits” could represent promising chemical starting points for the development and the optimization of new classes of therapeutics designed to target <i>Candida</i> biofilms. |
| first_indexed | 2024-03-10T13:44:56Z |
| format | Article |
| id | doaj.art-ceec82b2e02947d3a4ec901e1043cbea |
| institution | Directory Open Access Journal |
| issn | 2309-608X |
| language | English |
| last_indexed | 2024-03-10T13:44:56Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Fungi |
| spelling | doaj.art-ceec82b2e02947d3a4ec901e1043cbea2023-11-21T02:44:23ZengMDPI AGJournal of Fungi2309-608X2020-12-0171910.3390/jof7010009A Screen for Small Molecules to Target <i>Candida albicans</i> BiofilmsMatthew B. Lohse0Craig L. Ennis1Nairi Hartooni2Alexander D. Johnson3Clarissa J. Nobile4Department of Microbiology and Immunology, University of California—San Francisco, San Francisco, CA 94158, USAQuantitative and Systems Biology Graduate Program, University of California—Merced, Merced, CA 95343, USADepartment of Microbiology and Immunology, University of California—San Francisco, San Francisco, CA 94158, USADepartment of Microbiology and Immunology, University of California—San Francisco, San Francisco, CA 94158, USADepartment of Molecular and Cell Biology, School of Natural Sciences, University of California—Merced, Merced, CA 95343, USAThe human fungal pathogen <i>Candida albicans</i> can form biofilms on biotic and abiotic surfaces, which are inherently resistant to antifungal drugs. We screened the Chembridge Small Molecule Diversity library containing 30,000 “drug-like” small molecules and identified 45 compounds that inhibited biofilm formation. These 45 compounds were then tested for their abilities to disrupt mature biofilms and for combinatorial interactions with fluconazole, amphotericin B, and caspofungin, the three antifungal drugs most commonly prescribed to treat <i>Candida</i> infections. In the end, we identified one compound that moderately disrupted biofilm formation on its own and four compounds that moderately inhibited biofilm formation and/or moderately disrupted mature biofilms only in combination with either caspofungin or fluconazole. No combinatorial interactions were observed between the compounds and amphotericin B. As members of a diversity library, the identified compounds contain “drug-like” chemical backbones, thus even seemingly “weak hits” could represent promising chemical starting points for the development and the optimization of new classes of therapeutics designed to target <i>Candida</i> biofilms.https://www.mdpi.com/2309-608X/7/1/9high-throughput screensbiofilmsbiofilm inhibitionbiofilm disruption<i>Candida albicans</i>antimicrobial resistance |
| spellingShingle | Matthew B. Lohse Craig L. Ennis Nairi Hartooni Alexander D. Johnson Clarissa J. Nobile A Screen for Small Molecules to Target <i>Candida albicans</i> Biofilms Journal of Fungi high-throughput screens biofilms biofilm inhibition biofilm disruption <i>Candida albicans</i> antimicrobial resistance |
| title | A Screen for Small Molecules to Target <i>Candida albicans</i> Biofilms |
| title_full | A Screen for Small Molecules to Target <i>Candida albicans</i> Biofilms |
| title_fullStr | A Screen for Small Molecules to Target <i>Candida albicans</i> Biofilms |
| title_full_unstemmed | A Screen for Small Molecules to Target <i>Candida albicans</i> Biofilms |
| title_short | A Screen for Small Molecules to Target <i>Candida albicans</i> Biofilms |
| title_sort | screen for small molecules to target i candida albicans i biofilms |
| topic | high-throughput screens biofilms biofilm inhibition biofilm disruption <i>Candida albicans</i> antimicrobial resistance |
| url | https://www.mdpi.com/2309-608X/7/1/9 |
| work_keys_str_mv | AT matthewblohse ascreenforsmallmoleculestotargeticandidaalbicansibiofilms AT craiglennis ascreenforsmallmoleculestotargeticandidaalbicansibiofilms AT nairihartooni ascreenforsmallmoleculestotargeticandidaalbicansibiofilms AT alexanderdjohnson ascreenforsmallmoleculestotargeticandidaalbicansibiofilms AT clarissajnobile ascreenforsmallmoleculestotargeticandidaalbicansibiofilms AT matthewblohse screenforsmallmoleculestotargeticandidaalbicansibiofilms AT craiglennis screenforsmallmoleculestotargeticandidaalbicansibiofilms AT nairihartooni screenforsmallmoleculestotargeticandidaalbicansibiofilms AT alexanderdjohnson screenforsmallmoleculestotargeticandidaalbicansibiofilms AT clarissajnobile screenforsmallmoleculestotargeticandidaalbicansibiofilms |