A Selective Serotonin Reuptake Inhibitor, a Proton Pump Inhibitor, and Two Calcium Channel Blockers Inhibit Candida albicans Biofilms
Open accessAbstract
Biofilms formed by the human fungal pathogen Candida albicans are naturally resistant to many of the antifungal agents commonly used in the clinic. We screened a library containing 1600 clinically tested drug compounds to identify compounds that inhibit C. albicans biofilm formation. The compounds that emerged from the initial screen were validated in a secondary screen and then tested for (1) their abilities to disrupt mature biofilms and (2) for synergistic interactions with representatives of the three antifungal agents most commonly prescribed to treat Candida infections, fluconazole, amphotericin B, and caspofungin. Twenty compounds had antibiofilm activity in at least one of the secondary assays and several affected biofilms but, at the same concentration, had little or no effect on planktonic (suspension) growth of C. albicans. Two calcium channel blockers, a selective serotonin reuptake inhibitor, and an azole-based proton pump inhibitor were among the hits, suggesting that members of these three classes of drugs or their derivatives may be useful for treating C. albicans biofilm infections.
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Paroxetine promotes mitochondrial depolarization and membrane damage in yeast at 110-282 μM (40-101 μg/mL).
“| Paroxetine (third generation of selective serotonin reuptake inhibitors) | C. albicans, E. coli, A. baumanii | 110-282 µM (40-101 µg/mL) | Inhibits cell growth; promotes mitochondrial inhibits bacterial growth. depolarization and membrane damage in yeast, | [56,58,67-69] |”
From Antimicrobial Properties of Antidepressants and Antipsychotics—Possibilities and Implications (2021) · cites this paper as [69]
Paroxetine inhibits cell growth in C. albicans, E. coli, and A. baumanii at 110-282 μM (40-101 μg/mL).
“| Paroxetine (third generation of selective serotonin reuptake inhibitors) | C. albicans, E. coli, A. baumanii | 110-282 µM (40-101 µg/mL) | Inhibits cell growth; promotes mitochondrial inhibits bacterial growth. depolarization and membrane damage in yeast, | [56,58,67-69] |”
From Antimicrobial Properties of Antidepressants and Antipsychotics—Possibilities and Implications (2021) · cites this paper as [69]
Paroxetine inhibits bacterial growth at 110-282 μM (40-101 μg/mL).
“| Paroxetine (third generation of selective serotonin reuptake inhibitors) | C. albicans, E. coli, A. baumanii | 110-282 µM (40-101 µg/mL) | Inhibits cell growth; promotes mitochondrial inhibits bacterial growth. depolarization and membrane damage in yeast, | [56,58,67-69] |”
From Antimicrobial Properties of Antidepressants and Antipsychotics—Possibilities and Implications (2021) · cites this paper as [69]
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- Authors
- Nobile, C. J., Ennis, C. L., Hartooni, N., Johnson, A. D., & Lohse, M. B.
- Affiliations
- University of California, Merced (US)
- University of California, San Francisco (US)
- Corresponding author
- Lohse, Matthew B.
- Venue
- Microorganisms
- Publisher
- MDPI AG
- Published
- 2020-05-18
- Volume
- 8
- Issue
- 5
- Pages
- 756
- ISSN
- 2076-2607 (ISSN-L)
- PMC
- PMC7285287
- OpenAlex
- W3025579118
- Cited by
- 13
- References
- 58
- Citations by year
- 2025: 4 · 2022: 4 · 2021: 3 · 2020: 2
- FWCI
- 0.30
- Type
- journal article
- Language
- en
- Open access
- gold
- dx.doi.org
- Licence
- Locations
- Microorganisms (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- eScholarship (California Digital Library) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Funders
- National Institutes of Health (R35GM124594, R41AI112038, R01AI083311, R43AI131710, F31DE028488)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bacterial biofilms and quorum sensing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Keywords
- Candida albicans, biofilm inhibition, antifungal drug repurposing, selective serotonin reuptake inhibitors, proton pump inhibitors, calcium channel blockers, fluconazole, amphotericin B, caspofungin, drug synergy, antifungal resistance, planktonic growth
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