Cited by 52Fungal Infections and StudiesAntifungal resistance and susceptibilityPneumocystis jirovecii pneumonia detection and treatment

Atorvastatin as a promising anticryptococcal agent

Ribeiro, Noelly de Queiroz, Costa, Marliete Carvalho, Magalhães, Thaís Furtado Ferreira, Carneiro, Hellem Cristina Silva, Oliveira, Lorena Vívien, Fontes, Alide Caroline Lima, Santos, Julliana Ribeiro Alves, Ferreira, Gabriela Freitas +6 more·2017·International Journal of Antimicrobial Agents

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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Crossref · 10.1016/j.ijantimicag.2017.04.005

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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
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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