Abstract
Due to their antifungal activity, chitosan and its derivatives have potential to be used for treating yeast infections in humans. However, to be considered for use in human medicine, it is necessary to control and know the chemical composition of the compound, which is not always the case for polymeric chitosans. Here, we analyze the antifungal activity of a soluble and well-defined chito-oligosaccharide (CHOS) with an average polymerization degree (DPn) of 32 and fraction of acetylation (FA) of 0.15 (C32) on 52 medically relevant yeast strains. Minimal inhibitory concentrations (MIC) varied widely among yeast species, strains and isolates (from > 5000 to < 9.77 μg mL-1) and inhibition patterns showed a time- and dose-dependencies. The antifungal activity was predominantly fungicidal and was inversely proportional to the pH, being maximal at pH 4.5, the lowest tested pH. Furthermore, antifungal effects of CHOS fractions with varying average molecular weight indicated that those fractions with an intermediate degree of polymerization, i.e. DP 31 and 54, had the strongest inhibitory effects. Confocal imaging showed that C32 adsorbs to the cell surface, with subsequent cell disruption and accumulation of C32 in the cytoplasm. Thus, C32 has potential to be used as a therapy for fungal infections.
Highlights
The frequency of yeast infections in humans has increased during the last decades mostly due to the growing number of immunocompromised patients and to the emergence of antifungal resistance [1]
Candida albicans is often considered the predominant cause of invasive and superficial fungal infections, but the epidemiology of yeast infections is rapidly evolving and other yeasts have emerged as major opportunistic pathogens [2, 3]
The number of monomeric units defines the degree of polymerization (DP) of a chitosan, while the fraction of acetylation (FA) is a measure of the average number of GlcNAc relative to the sum of GlcN and GlcNAc
Summary
The frequency of yeast infections in humans has increased during the last decades mostly due to the growing number of immunocompromised patients and to the emergence of antifungal resistance [1]. Chitosan is composed of a variable number of β-(1–4) linked units of 2-acetamide-2-deoxy-β-d-glucopyranose (GlcNAc) and 2-amino-2-deoxy-β-d-glycopyranose (GlcN) [5]. The number of monomeric units defines the degree of polymerization (DP) of a chitosan, while the fraction of acetylation (FA) is a measure of the average number of GlcNAc relative to the sum of GlcN and GlcNAc. Both, FA and DP are fundamental for some key physical-chemical properties, including solubility and conformation [6,7,8]. Obtaining well-defined CHOS preparations, especially preparations of longer CHOS (DPn > 10) is not straightforward
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