Are the Statins promising antifungal agents against invasive candidiasis? - 16/02/19
, Lídia Anita Alves-Nascimento a, Jéssica Tauany Andrade a, Letícia Vieira b, d, Rosy Iara Maciel de Azambuja Ribeiro c, Ralph Gruppi Thomé d, Hélio Batista dos Santos d, Jaqueline Maria Siqueira Ferreira a, Adriana Cristina Soares bBienvenue sur EM-consulte, la référence des professionnels de santé.
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| pages | 12 |
| Iconographies | 6 |
| Vidéos | 0 |
| Autres | 0 |
Graphical abstract |
Highlights |
• | Fluvastatin, atorvastatin and rosuvastatin show high antifungal activity in vitro. |
• | Statins interact synergistically with fluconazole, itraconazole, and ketoconazole. |
• | Cell wall and ergosterol are not targets of the antifungal action of statins. |
• | Yeast-to-hyphal transition and biofilm generation are induced by statins. |
• | Fluvastatin stimulates the invasion of C. albicans to extra-hepatic sites in a mouse model of intra-abdominal candidiasis. |
Abstract |
The medical importance of intra-abdominal candidiasis (IAC) contrasts with the limited number of pharmacological treatment options available and the increasing rate of resistance to antifungal drugs. Thus, the repositioning of compounds in clinical use can contribute to the broadening of treatment possibilities for this infection. Statins, a class of drugs used to reduce cardiovascular event risk, have shown antiparasitic, antibacterial, and antiviral activities; however, their antifungal effects remain poorly studied. In this context, the present study aimed to elucidate the antifungal potential of six statins in vitro, as well as to evaluate the therapeutic use of fluvastatin in a mouse model of IAC. The biological effects of statins were evaluated against Candida spp., through the determination of the minimum inhibitory concentration (MIC). For the statins that showed activity, the fungicidal concentration, toxicity/selectivity, synergism with azoles and polyenes, phenotypic effects, and activity against virulence factors were also determined. Atorvastatin, rosuvastatin and fluvastatin were highly active, especially against C. albicans (MIC < 1–128 μg.mL−1) and C. glabrata (MIC 32–64 μg.mL−1). Fluvastatin and atorvastatin were selective for C. albicans in baby hamster kidney (BHK) cells. Moreover, all active statins in the antifungal assay showed high selectivity for fungal cells over bacteria. The combination of atorvastatin, rosuvastatin, and fluvastatin with azoles was associated with a synergistic effect. Active statins do not act on the fungal membrane or wall, but instead stimulate farnesol-dependent pathogenicity factors such as yeast-to-hyphal transition and biofilm generation. Fluvastatin treatment was evaluated in a mouse model of IAC, showing stimulation of the extra-hepatic dissemination of C. albicans but improvements in renal, splenic, and hepatic histological aspects. In conclusion, statins have potent antifungal activity in vitro, but the therapeutic effect in vivo is restricted to their anti-inflammatory activity.
Le texte complet de cet article est disponible en PDF.Keywords : Candida albicans, Biofilm, Yeast-to-hyphal transition, Synergism, Fluvastatin, Intra-abdominal candidiasis
Plan
Vol 111
P. 270-281 - mars 2019 Retour au numéro
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