Abstract
BackgroundThe echinocandins are lipopeptides that can be employed as antifungal drugs that inhibit the synthesis of 1,3-β-glucans within the fungal cell wall. Anidulafungin and caspofungin are echinocandins used in the treatment of Candida infections and have activity against other fungi including Aspergillus fumigatus. The echinocandins are generally considered fungistatic against Aspergillus species.MethodsCulture of A. fumigatus from conidia to microcolonies on a support of porous aluminium oxide (PAO), combined with fluorescence microscopy and scanning electron microscopy, was used to investigate the effects of anidulafungin and caspofungin. The PAO was an effective matrix for conidial germination and microcolony growth. Additionally, PAO supports could be moved between agar plates containing different concentrations of echinocandins to change dosage and to investigate the recovery of fungal microcolonies from these drugs. Culture on PAO combined with microscopy and image analysis permits quantitative studies on microcolony growth with the flexibility of adding or removing antifungal agents, dyes, fixatives or osmotic stresses during growth with minimal disturbance of fungal microcolonies.SignificanceAnidulafungin and caspofungin reduced but did not halt growth at the microcony level; additionally both drugs killed individual cells, particularly at concentrations around the MIC. Intact but not lysed cells showed rapid recovery when the drugs were removed. The classification of these drugs as either fungistatic or fungicidal is simplistic. Microcolony analysis on PAO appears to be a valuable tool to investigate the action of antifungal agents.
Highlights
The echinocandins are an important class of lipopeptide antifungal compounds consisting of cyclic hexapeptides linked to a long chain fatty acid
Conidia purified from clinical isolates and a reference strains (ATCC204305) of A. fumigatus and A. terreus (Tables 1 and 2) were inoculated onto 3668 mm strips of porous aluminium oxide (PAO) placed on Sabouraud agar to a density of from 5 to 50 cfu/mm2
This suggests conidia can be inoculated to single cfu on PAO and germination occurs with the same efficiency to that seen on agar
Summary
The echinocandins are an important class of lipopeptide antifungal compounds consisting of cyclic hexapeptides linked to a long chain fatty acid. The echinocandins inhibit cell wall synthesis, by non-competitive inhibition of the 1,3-b-glucan synthase. This is thought to occur via interaction with the Fks subunit of this enzyme [1]. Echinocandins are commonly used to treat infections by many Candida species, against which they are fungicidal. Unlike an earlier class of 1,3-beta-glucan synthase inhibitors, the liposaccharide papulocandins, the activity of echinocandins extends beyond Candida spp., to include Aspergillus spp. and Pneumocystis carinii [2]. The echinocandins are lipopeptides that can be employed as antifungal drugs that inhibit the synthesis of 1,3b-glucans within the fungal cell wall. Anidulafungin and caspofungin are echinocandins used in the treatment of Candida infections and have activity against other fungi including Aspergillus fumigatus.
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