明确的壳寡糖制剂对医学相关酵母的抗真菌活性。
Antifungal activity of well-defined chito-oligosaccharide preparations against medically relevant yeasts.
机构信息
Department of Chemistry, Biotechnology, and Food Science, Norwegian University of Life Sciences, Aas, Norway.
Institute of Clinical Medicine, Department of Microbiology, University of Oslo, Blindern, Oslo, Norway.
出版信息
PLoS One. 2019 Jan 8;14(1):e0210208. doi: 10.1371/journal.pone.0210208. eCollection 2019.
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.
由于其抗真菌活性，壳聚糖及其衍生物有可能被用于治疗人类的酵母感染。然而，要考虑将其用于人类医学，就必须控制和了解该化合物的化学组成，而对于聚合壳聚糖来说，并非总是如此。在这里，我们分析了一种具有平均聚合度（DPn）为 32 和乙酰化分数（FA）为 0.15（C32）的可溶性和明确的壳寡糖（CHOS）对 52 种具有医学相关性的酵母菌株的抗真菌活性。最小抑菌浓度（MIC）在酵母种、菌株和分离株之间差异很大（> 5000 至 < 9.77 μg mL-1），并且抑制模式表现出时间和剂量依赖性。抗真菌活性主要是杀菌性的，并且与 pH 值成反比，在 pH 值为 4.5 时达到最大值，这是测试的最低 pH 值。此外，具有不同平均分子量的 CHOS 级分的抗真菌作用表明，那些具有中等聚合度的级分，即 DP 31 和 54，具有最强的抑制作用。共焦成像显示，C32 吸附在细胞表面，随后细胞破裂，C32 积累在细胞质中。因此，C32 有可能被用作治疗真菌感染的药物。
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