Chemical and physical modulation of antibiotic activity in emericella species.

The addition of epigenetic modifying agents and ion-exchange resins to culture media and solid-state fermentations have been promoted as ways to stimulate expression of latent biosynthetic gene clusters and to modulate secondary metabolite biosynthesis. We asked how combination of these treatments would affect a population of screening isolates and their patterns of antibiosis relative to fermentation controls. A set of 43 Emericella strains, representing 25 species and varieties, were grown on a nutrient-rich medium comprising glucose, casein hydrolysate, urea, and mineral salts. Each strain was grown in untreated agitated liquid medium, a medium treated with suberoylanilide hydroxamic acid, a histone deacetylase inhibitor, 5-azacytidine, a DNA methylation inhibitor, an Amberlite non-ionic polyacrylate resin, and the same medium incorporated into an inert static vermiculite matrix. Species-inherent metabolic differences more strongly influenced patterns of antibiosis than medium treatments. The antibacterial siderophore, desferritriacetylfusigen, was detected in most species in liquid media, but not in the vermiculite medium. The predominant antifungal component detected was echinocandin B. Some species produced this antifungal regardless of treatment, although higher quantities were often produced in vermiculite. Several species are reported for the first time to produce echinocandin B. A new echinocandin analog, echinocandin E, was identified from E. quadrilineata.

Nuevos antifúngicos: Las equinocandinas / New antifungal agents: Echinocandins

La familia de lipopéptidos conocidos como equinocandinas emerge como las nuevas "penicilinas antifúngicas", capaces de destruir la pared celular micótica al inhibir la síntesis del glucano, fundamental constituyente de la estructura fúngica. Las equinocandinas han mostrado in vitro e in vivo, ser fungicidas contra la mayoría de las especies de Candida y fungistáticas contra Aspergillus sp, sin exhibir acción sobre células de mamíferos. Tres agentes emergen como los principales representantes de esta clase; caspofungina, micafungina y anidulafungina, estando las dos primeras ya licenciadas para su uso en humanos. Su óptimo perfil de seguridad, con baja incidencia y severidad de efectos adversos, cómoda posología y pocas interacciones con otros fármacos, representan notables ventajas para la terapéutica antifúngica moderna. Comparativamente han mostrado tener eficacia clínica similar a anfotericina B, sin la toxicidad que este polieno tradicionalmente muestra, lo que sumado a la ausencia de antagonismo con otros antifúngicos permite sugerir que la terapia combinada pudiera ser un nuevo estándar de manejo para la tan temida aspergilosis invasora.

The lipopeptide family known as echinocandins emerge as the new "antifungal penicillins", because their ability to destroy the fungal cell wall as they inhibit glucan synthesis, the main component of fungal structure. Echinocandins are fungicidal in vitro and in vivo against most Candida species and fungistatic against Aspergillus sp, without antifungal activity over mammal cells. Three drugs are representative of this class; caspofungin, micafungin and anidulafungin, the two first have been licensed for human use. Their optimal security profile, with low incidence and severity of adverse effects, kind posology and few interactions with other drugs, represent noticeable advantages for modern antifungal therapy. They have similar clinical efficacy as amphotericin B, without its toxicity, which besides the absence of antagonism with other antifungal drugs, allows to suggest that combined antifungal therapy could represent a new standard for the management of the feared invasive aspergillosis.