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Candidiasis is the most common opportunistic yeast infection, with Candida albicans as a paramount causative species. (1,3)-β-D-glucan is one of the three main targets of clinically available antifungal agents used to treat Candida infections. It is one of the most abundant fungal cell wall components. Echinocandins represent the newest class of antifungals affecting cell wall biosynthesis through non-competitive inhibition of (1,3)-β-D-glucan synthase. Therefore, treatment with echinocandins causes defects in fungal cell integrity. In the present study, similar activity of emodin (6-methyl-1,3,8-trihydroxyanthraquinone) has been revealed. Many reports have already shown the antifungal potential of this pleiotropic molecule, including its activity against C. albicans. The aim of this report was to evaluate the activity of emodin towards a new molecular target, i.e. (1,3)-β-D-glucan synthase isolated from Candida cells. Moreover, given the identical mechanism of the activity of both molecules, interaction of emodin with caspofungin was determined. The study revealed that emodin reduced (1,3)-β-D-glucan synthase activity and increased cell wall damage, which was evidenced by both a sorbitol protection assay and an aniline blue staining assay. Furthermore, the synergy testing method showed mainly independence of the action of both tested antifungal agents, i.e. emodin and caspofungin used in combination.
Candida sp. may be regarded as one of the leading etiologic agents of hospital-acquired infections, including those related with the indwelling medical devices, which become colonized by the yeasts, accompanied by biofilm formation. In this paper we assayed in vitro susceptibility to caspofungin of planktonic and sessile cells of nasopharyngeal isolates of Candida sp. Two types of biomaterials were used - silicone elastomer-coated latex urinary Foley catheter and PCV Thorax catheter. The minimal inhibitory concentrations (MIC) of caspofungin for planktonic Candida sp. cells ranged from 0.008 to 0.031 mg/l, while the minimal fungicidal concentrations (MFC) from 0.008 to 0.062 mg/l, with MFC/MIC ratios ≤2. The minimal concentration of caspofungin preventing adhesion process of Candida sp. on both biomaterials ranged from 0.004 to 0.031 mg/l, while preventing biofilm formation from 0.004 to 0.062 mg/l. In contrast, much higher minimal concentrations of caspofungin were needed to eradicate the mature biofilm (0.25 to >8 mg/l). In all cases, drug concentrations depended on the strain and the biomaterial used. Our preliminary data suggest that caspofungin, showing good anti-adherent activity in vitro against Candida sp., appears to be a potential agent rather for prophylaxis of the yeast infections associated with biomaterials but not for their treatment.
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