The DOI matches its Crossref record; 43 of the 44 references it cites were found in a registry or an index.
The Antidepressant Sertraline Provides a Promising Therapeutic Option for Neurotropic Cryptococcal Infections
Open accessAbstract
Therapeutic treatment for systemic mycoses is severely hampered by the extremely limited number of antifungals. The difficulty of treatment of fungal infections in the central nervous system is further compounded by the poor central nervous system (CNS) penetration of most antifungals due to the blood-brain barrier. Only a few fungistatic azole drugs, such as fluconazole, show reasonable CNS penetration. Here we demonstrate that sertraline (Zoloft), the most frequently prescribed antidepressant, displays potent antifungal activity against Cryptococcus neoformans , the major causative agent of fungal meningitis. In in vitro assays, this neurotropic drug is fungicidal to all natural Cryptococcus isolates tested at clinically relevant concentrations. Furthermore, sertraline interacts synergistically or additively with fluconazole against Cryptococcus . Importantly, consistent with our in vitro observations, sertraline used alone reduces the brain fungal burden at an efficacy comparable to that of fluconazole in a murine model of systemic cryptococcosis. It works synergistically with fluconazole in reducing the fungal burden in brain, kidney, and spleen. In contrast to its potency against Cryptococcus , sertraline is less effective against strains of Candida species and its interactions with fluconazole against Candida strains are often antagonistic. Therefore, our data suggest the unique application of sertraline against cryptococcosis. To understand the antifungal mechanisms of sertraline, we screened a whole-genome deletion collection of Saccharomyces cerevisiae for altered sertraline susceptibility. Gene ontology analyses of selected mutations suggest that sertraline perturbs translation. In vitro translation assays using fungal cell extracts show that sertraline inhibits protein synthesis. Taken together, our findings indicate the potential of adopting this antidepressant in treating cryptococcal meningitis.
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In the citing paper
“In addition, several psychotherapeutic agents such as fluoxetine, fluphenazine (FNZ), or sertraline can enhance FLC activity against fungal species 14,15 .”
From Antifungal tolerance is a subpopulation effect distinct from resistance and is associated with persistent candidemia (2018) · cites this paper as [15]
Experimental — accuracy not yet measuredIn the citing paper
“Sertraline was initially demonstrated to be able to potentiate the action of azoles against cryptococcal microbes [60]; later, it was tested in a Phase II study [94] and a follow-up Phase III study in HIV patients infected by this fungus, but with no convincing results [95].”
From Antimicrobial Properties of Antidepressants and Antipsychotics—Possibilities and Implications (2021) · cites this paper as [60]
In the citing paper
“Originally developed as an antidepressant, sertraline acts synergistically with fluconazole in a mouse model of systemic cryptococcosis, reducing the fungal burden105.”
From Treatment strategies for cryptococcal infection: challenges, advances and future outlook (2021) · cites this paper as [105]
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Cites
Functional Characterization of the S. cerevisiae Genome by Gene Deletion and Parallel Analysis
Winzeler, E. A., Shoemaker, D. D., Astromoff, A., Liang, H., Anderson, K., Andre, B., Bangham, R., Benito, R., Boeke, J. D., Bussey, H., et al. (1999) · Science · doi:10.1126/science.285.5429.901 · Cited by 3,953
Perfect, J. R., Dismukes, W. E., Dromer, F., Goldman, D. L., Graybill, J. R., Hamill, R. J., Harrison, T. S., Larsen, R. A., Lortholary, O., Nguyen, M.-H., et al. (2010) · Clinical Infectious Diseases · doi:10.1086/649858 · Cited by 2,660
Park, B. J., Wannemuehler, K. A., Marston, B. J., Govender, N. P., Pappas, P. G., & Chiller, T. M. (2009) · AIDS · doi:10.1097/qad.0b013e328322ffac · Cited by 2,062
Recent findings on the viable but nonculturable state in pathogenic bacteria.
Oliver, J. (2010) · FEMS Microbiology Reviews · doi:10.1111/j.1574-6976.2009.00200.x · Cited by 1,231
Cryptococcosis in the era of AIDS--100 years after the discovery of Cryptococcus neoformans
Mitchell, T. G., & Perfect, J. R. (1995) · Clinical Microbiology Reviews · doi:10.1128/cmr.8.4.515 · Cited by 1,213
Pharmacokinetics of selective serotonin reuptake inhibitors
Hiemke, C., & Härtter, S. (2000) · Pharmacology & Therapeutics · doi:10.1016/s0163-7258(99)00048-0 · Cited by 887
Amphotericin B: side effects and toxicity
Laniado-Laborín, R., & Cabrales-Vargas, M. N. (2009) · Revista Iberoamericana de Micología · doi:10.1016/j.riam.2009.06.003 · Cited by 739
Casadevall, A., & Perfect, J. R. (1998) · ASM Press eBooks · doi:10.1128/9781555818241 · Cited by 697
Drug and chemical blood-level data 2001
Winek, C. L., Wahba, W. W., Winek, C. L., & Winek, T. A. (2001) · Forensic Science International · doi:10.1016/s0379-0738(01)00483-2 · Cited by 367
Identifying off-target effects and hidden phenotypes of drugs in human cells
MacDonald, M. L., Lamerdin, J. E., Owens, S., Keon, B. H., Bilter, G. K., Shang, Z., Huang, Z., Yu, H. W., Dias, J., Minami, T., et al. (2006) · Nature Chemical Biology · doi:10.1038/nchembio790 · Cited by 294
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Items 201–205 of 205
Severe Pulmonary Coccidioidomycosis Treated With Systemic Corticosteroids in an Adolescent Child
Shinozaki, R. M., Krogstad, P. A., Adachi, K., & Bulut, Y. (2026) · Case Reports in Pediatrics · doi:10.1155/crpe/6010113
Alkashef, N. M., Khan, A. A., & Seleem, M. N. (2026) · PLoS neglected tropical diseases · doi:10.1371/journal.pntd.0014627
Śnieżek, J., & Polak-Szczybyło, E. (2026) · Nutrients · doi:10.3390/nu18182940
Ayala, M., Jakamartana, A., Costa, R. M. D. S., Cheung, E. C.-K., Bednarek, J. M., Moreau, C. T., & Brown, J. C. S. (2026) · mSphere · doi:10.1128/msphere.00432-26
Sertraline as a Treatment Option for Fungal Infections: A Systematic Review
Cárdenas, C. D. S., Alcázar-Olaiz, M. D., Fuentes‐Venado, C. E., Loza-Mejía, M. A., Cruz-López, N. G., Arenas, R., Bonifáz, A., Pinto‐Almazán, R., & Martínez-Herrera, E. O. (2026) · Current Fungal Infection Reports · doi:10.1007/s12281-026-00541-2
Metadata
- Authors
- Zhai, B., Wu, C., Wang, L., Sachs, M. S., & Lin, X.
- Affiliations
- Texas A&M University (US)
- Venue
- Antimicrobial Agents and Chemotherapy
- Publisher
- American Society for Microbiology
- Published
- 2012-07
- Volume
- 56
- Issue
- 7
- Pages
- 3758-3766
- ISSN
- 0066-4804 (ISSN-L)
- 1098-6596
- PMC
- PMC3393448
- OpenAlex
- W2172160469
- Cited by
- 205
- References
- 44
- Citations by year
- 2026: 12 · 2025: 13 · 2024: 19 · 2023: 18 · 2022: 18 · 2021: 13 · 2020: 21 · 2019: 24 · 2018: 12 · 2017: 15 · 2016: 18 · 2015: 9 · 2014: 6 · 2013: 5 · 2012: 2
- FWCI
- 5.25
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Antimicrobial Agents and Chemotherapy (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- OakTrust (Texas A&M University Libraries) (submittedVersion)
- Funders
- American Heart Association
- Johns Hopkins University
- National Institute of General Medical Sciences (R01GM47498, R01GM047498)
- National Institute of Allergy and Infectious Diseases (R01AI097599)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Fungal Infections and Studies
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Fungal Plant Pathogen Control
- Keywords
- sertraline, Cryptococcus neoformans, cryptococcosis, cryptococcal meningitis, antifungal activity, fluconazole, drug synergy, drug repurposing, antidepressants, Candida, protein synthesis inhibition, blood-brain barrier, systemic fungal infection
- MeSH terms
- Animals, Antidepressive Agents, Cryptococcosis, Cryptococcus neoformans, Female, Microbial Sensitivity Tests, Saccharomyces cerevisiae, Fluconazole, Sertraline, Mice
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