Atorvastatin as a promising anticryptococcal agent
Abstract
Cryptococcosis caused by Cryptococcus gattii leads to pneumonia and meningoencephalitis, and has a high mortality rate worldwide due to the inadequacy of available therapy and increasing drug resistance. There is a need to develop effective treatments, and drug repositioning is an interesting alternative to achieve new strategies to treat cryptococcosis. Atorvastatin (ATO), a statin currently used to treat hypercholesterolaemia, was tested in this study as an adjuvant to control infections caused by C. gattii. Several aspects of the effect of ATO on the host and the yeast were evaluated, with particular focus on the association of ATO with fluconazole (FLC), which (i) reduced ergosterol content in the cell membrane and altered properties of the polysaccharide capsule of C. gattii; (ii) increased the production of reactive oxygen species by macrophages; and (iii) reduced yeast phagocytosis and the intracellular proliferation rate. In an animal model, infected mice treated with ATO + FLC showed increased survival, improved clinical condition, and reduced fungal burden in the lungs and brain. This study is the first to perform in vivo tests with ATO + FLC for the treatment of cryptococcosis. The results suggest that ATO may be an important adjuvant for the treatment of cryptococcosis.
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Reposicionamento de fármacos para o tratamento de criptococose
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Influence of the agrochemical benomyl on Cryptococcus gattii-plant interaction in vitro and in vivo
Dornelas, J. C. M., Paixão, V. M., do Carmo, P. H. F., da Costa, M. C., Gomes, E. C. Q., de Resende, M. A., & Santos, D. A. (2024) · Brazilian Journal of Microbiology · doi:10.1007/s42770-024-01440-9
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- Authors
- Ribeiro, N. D. Q., Costa, M. C., Magalhães, T. F. F., Carneiro, H. C. S., Oliveira, L. V., Fontes, A. C. L., Santos, J. R. A., Ferreira, G. F., Araujo, G. R. D. S., Alves, V., Frases, S., Paixão, T. A., de Resende Stoianoff, M. A., & Santos, D. A.
- Affiliations
- Universidade Federal de Minas Gerais (BR)
- Universidade Federal de Juiz de Fora (BR)
- Universidade Federal do Rio de Janeiro (BR)
- Corresponding author
- Santos, Daniel Assis
- ORCID
- Venue
- International Journal of Antimicrobial Agents
- Publisher
- Elsevier BV
- Published
- 2017-06
- Volume
- 49
- Issue
- 6
- Pages
- 695-702
- ISSN
- 0924-8579 (ISSN-L)
- OpenAlex
- W2608596682
- Cited by
- 51
- References
- 41
- Citations by year
- 2025: 6 · 2024: 4 · 2023: 5 · 2022: 8 · 2021: 8 · 2020: 7 · 2019: 8 · 2018: 4 · 2017: 1
- FWCI
- 4.29
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- International Journal of Antimicrobial Agents (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—CAPES and Fundação de Amparo a Pesquisa do Estado de Minas Gerais—FAPEMIG (PPM-00117-14)
- Conselho Nacional de Desenvolvimento Científico e Tecnológico (305154/2014-1)
- Topics
- Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Health Sciences › Medicine › Epidemiology › Pneumocystis jirovecii pneumonia detection and treatment
- Keywords
- atorvastatin, Cryptococcus gattii, cryptococcosis, drug repurposing, statins, ergosterol, polysaccharide capsule, reactive oxygen species, macrophages, phagocytosis, meningoencephalitis, fungal pneumonia
- MeSH terms
- Atorvastatin, Animals, Anticholesteremic Agents, Antifungal Agents, Cryptococcosis, Disease Models, Animal, Drug Therapy, Combination, Male, Mice, Inbred C57BL, Fluconazole, Survival Analysis, Treatment Outcome, Cryptococcus gattii, Drug Repositioning
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