PROIMI   05436
PLANTA PILOTO DE PROCESOS INDUSTRIALES MICROBIOLOGICOS
Unidad Ejecutora - UE
artículos
Título:
Synergistic antifungal activity of statin-azoles associations as witnessed by Saccharomyces cerevisiae and Candida utilis bioassays and ergosterol quantification.
Autor/es:
CABRAL MARÍA EUGENIA; CASTELLANOS DE FIGUEROA, LUCÍA INÉS; FARIÑA J.I.
Revista:
REVISTA IBEROAMERICANA DE MICOLOGIA
Editorial:
ASOCIACION ESPANOLA MICOLOGIA-AEM
Referencias:
Lugar: Madrid; Año: 2013 vol. 30 p. 31 - 38
ISSN:
1130-1406
Resumen:
Frequent opportunist fungal infections and the resistance to available antifungal drugspromoted the development of new alternatives for treatment, like antifungal drug 29combinations. This work aimed to detect the antifungal synergism between statins and azoles 30by means of an agar-well diffusion bioassay with Saccharomyces cerevisiae ATCC 32051 31and Candida utilis Pr1-2 as test strains. Growth inhibition was significantly increased when 32clotrimazole, fluconazole, itraconazole, ketoconazole and miconazole were combined with 33atorvastatin, lovastatin, rosuvastatin and simvastatin. Highest growth inhibition increments 34on S. cerevisiae (77.5%) or C. utilis (43.2%) were observed with a sub-inhibitory 35concentration of simvastatin plus a minimal inhibitory concentration of miconazole, i.e. 4 + 362.4 µg ml-1 or 20 + 4.8 µg ml-1, respectively. Pravastatin had almost no significant effects (0- 377.6% inhibition increment). Highest interaction ratios between antifungal agents (2.2-3) 38corresponded to simvastatin-miconazole combinations and were indicative of synergism. 39Synergism was also confirmed by the increased reduction in cellular sterols levels (ca. 20%). 40Statin-induced ergosterol synthesis blockage was corroborated by means of ergosterol rescue 41bioassays, being pravastatin the easiest inhibition to be abolished whilst rosuvastatin, the 42most ergosterol-refractory. Selected statin-azole combinations might be viable alternatives 43for the therapeutic management of mycosis at lower administration doses or with higher 44efficiency. 4546