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热带假丝酵母表型转换:与潜在毒力特性修饰和抗真菌药物敏感性的关联。

Phenotypic switching in Candida tropicalis: association with modification of putative virulence attributes and antifungal drug sensitivity.

机构信息

Department of Microbiology, Paraná State University at Londrina.

出版信息

Med Mycol. 2014 Jan;52(1):106-14. doi: 10.3109/13693786.2013.825822.

DOI:10.3109/13693786.2013.825822
PMID:23971864
Abstract

Although Candida tropicalis has become an increasingly important human pathogen, little is known regarding its potential to cause disease. In this study we evaluated the phenotypic switching ability of C. tropicalis and analyzed the effect of switching on biological properties related to virulence factors. We demonstrated that C. tropicalis switched spontaneously, reversibly and at high frequency (10(-1) to 10(-3)) when grown on yeast extract-peptone-D-glucose (YPD) agar medium. Phenotypic switching in five clinical isolates of C. tropicalis resulted in colonies exhibiting the following morphologies: crepe, rough, crater, irregular center, mycelial and diffuse. The majority of the variant colonies were associated with higher percentages of filamentous growth relative to their parental unswitched isolates. Significant differences (P < 0.05) in the production of hemolytic factor were found between most of the switched variants and their respective parental counterparts. Variant colonies exhibiting the crepe (derived from isolates 49.07 and 100.10) and rough phenotype (derived from isolate 49.07) had higher biofilm formation than their parental counterparts exhibiting a smooth dome surface (P < 0.05). Our data revealed that switching was correlated with changes in the in vitro minimum inhibitory concentrations (MICs) of a subset of the switched variants phenotypes to itraconazole. While the MIC to itraconazole was higher for crepe variant compared with its parental isolate 49.07, the rough variant of 100.10 had a lower MIC to this antifungal agent. The presented data support the role of phenotypic switching in promoting changes in phenotypic expression of putative virulence traits and itraconazole susceptibility of clinical isolates of C. tropicalis.

摘要

虽然热带假丝酵母已成为一种日益重要的人类病原体,但人们对其致病潜力知之甚少。在这项研究中,我们评估了热带假丝酵母的表型转换能力,并分析了转换对与毒力因子相关的生物学特性的影响。我们证明,热带假丝酵母在酵母提取物-胰蛋白胨-葡萄糖(YPD)琼脂培养基上生长时,会自发、可逆且高频(10(-1) 到 10(-3))地发生表型转换。在五个热带假丝酵母临床分离株中,表型转换导致了以下形态的菌落:绉状、粗糙、火山口状、不规则中心、菌丝状和弥漫状。与未转换的亲本分离株相比,大多数变体菌落的丝状生长比例更高。在溶血因子的产生方面,大多数转换变体与相应的亲本分离株之间存在显著差异(P < 0.05)。与表现光滑穹顶表面的亲本分离株相比,表现绉状(来源于分离株 49.07 和 100.10)和粗糙表型(来源于分离株 49.07)的变体菌落的生物膜形成能力更高(P < 0.05)。我们的数据表明,转换与部分转换变体表型的体外最小抑菌浓度(MIC)的变化相关联,这些变体表型对伊曲康唑的敏感性发生了变化。虽然与亲本分离株 49.07 相比,绉状变体的伊曲康唑 MIC 更高,但 100.10 的粗糙变体对这种抗真菌药物的 MIC 更低。所呈现的数据支持表型转换在促进热带假丝酵母临床分离株的表型表达和伊曲康唑敏感性的潜在毒力特性变化中的作用。

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