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杀伤性酵母异常威克汉姆酵母 Cf20 通过产生杀伤毒素和挥发性化合物发挥广谱抗念珠菌活性。

The killer yeast Wickerhamomyces anomalus Cf20 exerts a broad anti-Candida activity through the production of killer toxins and volatile compounds.

机构信息

Instituto Superior de Investigaciones Biológicas (INSIBIO, CONICET-UNT) e Instituto de Química Biológica "Dr. Bernabé Bloj," Facultad de Bioquímica, Química y Farmacia, Universidad Nacional de Tucumán, Chacabuco 461, San Miguel de Tucumán. Argentina.

Centro de referencia para lactobacilos (CERELA, CONICET), Chacabuco 145, 4000, Tucumán, Argentina.

出版信息

Med Mycol. 2020 Nov 10;58(8):1102-1113. doi: 10.1093/mmy/myaa011.

Abstract

Candidiasis is a group of opportunistic infections caused by yeast of the genus Candida. The appearance of drug resistance and the adverse effects of current antifungal therapies require the search for new, more efficient therapeutic alternatives. Killer yeasts have aroused as suitable candidates for mining new antifungal compounds. Killer strains secrete antimicrobial proteins named killer toxins, with promissory antifungal activity. Here we found that the killer yeast Wickerhamomyces anomalus Cf20 and its cell-free supernatant (CFS) inhibited six pathogenic strains and one collection strain of Candida spp. The inhibition is mainly mediated by secreted killer toxins and, to a lesser extent, by volatile compounds such as acetic acid and ethyl acetate. A new large killer toxin (>180 kDa) was purified, which exerted 70-74% of the total CFS anti-Candida activity, and the previously described glucanase KTCf20 was inhibitory in a lesser extent as well. In addition, we demonstrated that Cf20 possesses the genes encoding for the β-1,3-glucanases WaExg1 and WaExg2, proteins with extensively studied antifungal activity, particularly WaExg2. Finally, the 10-fold concentrated CFS exerted a high candidacidal effect at 37°C, completely inhibiting the fungal growth, although the nonconcentrated CFS (RCF 1) had very limited fungistatic activity at this temperature. In conclusion, W. anomalus Cf20 produces different low and high molecular weight compounds with anti-Candida activity that could be used to design new therapies for candidiasis and as a source for novel antimicrobial compounds as well.

摘要

假丝酵母是一组由假丝酵母属的酵母引起的机会性感染。目前抗真菌治疗的耐药性出现和不良反应需要寻找新的、更有效的治疗替代方法。杀伤酵母作为挖掘新抗真菌化合物的合适候选者引起了关注。杀伤菌株分泌抗菌蛋白,称为杀伤毒素,具有有前途的抗真菌活性。在这里,我们发现杀伤酵母异常威克汉姆酵母 Cf20 及其无细胞上清液(CFS)抑制了六种致病性念珠菌属菌株和一种念珠菌属菌株。抑制主要由分泌的杀伤毒素介导,在较小程度上由挥发性化合物如乙酸和乙酸乙酯介导。一种新的大型杀伤毒素(>180 kDa)被纯化,其发挥了 70-74%的 CFS 抗念珠菌活性,而之前描述的葡聚糖酶 KTCf20 也具有抑制作用,但程度较小。此外,我们证明 Cf20 具有编码β-1,3-葡聚糖酶 WaExg1 和 WaExg2 的基因,这些基因编码的蛋白具有广泛研究的抗真菌活性,特别是 WaExg2。最后,浓缩 10 倍的 CFS 在 37°C 时对念珠菌具有很高的杀菌作用,完全抑制真菌生长,尽管未浓缩的 CFS(RCF 1)在该温度下几乎没有抑菌活性。总之,异常威克汉姆酵母 Cf20 产生具有抗念珠菌活性的不同低分子量和高分子量化合物,可用于设计念珠菌病的新疗法,也可作为新型抗菌化合物的来源。

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