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FLO8 缺失导致 Candida glabrata 的黏附力和毒力下降,同时下调了 EPA1、EPA6 和 EPA7 的表达。

FLO8 deletion leads to decreased adhesion and virulence with downregulated expression of EPA1, EPA6, and EPA7 in Candida glabrata.

机构信息

Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Department of Laboratory Medicine, Ruijin Hospital Luwan Branch, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

出版信息

Braz J Microbiol. 2022 Jun;53(2):727-738. doi: 10.1007/s42770-022-00703-7. Epub 2022 Feb 5.

Abstract

BACKGROUND

The Candida glabrata does not develop into a pathogenic hiphal form; however, it has become the second most common pathogen of fungal infections in humans, partly because of its adhesion ability and virulence.

OBJECTIVES

The present study aimed to determine whether Flo8, a transcription factor that plays an important role in the virulence and drug resistance in Candida albicans, has a similar role in C. glabrata.

METHODS

We constructed FLO8 null strains of a C. glabrata standard strain and eight clinical strains from different sources, and a FLO8 complemented strain. Real-time quantitative PCR, biofilm formation assays, hydrophobicity tests, adhesion tests, Caenorhabditis elegans survival assay, and drug-susceptibility were then performed.

RESULTS

Compared with the wild-type strains, the biofilm formation, hydrophobicity, adhesion, and virulence of the FLO8-deficient strains decreased, accompanied by decreased expression of EPA1, EPA6, and EPA7. On the other hand, it showed no changes in antifungal drug resistance, although the expression levels of CDR1, CDR2, and SNQ2 increased after FLO8 deletion.

CONCLUSIONS

These results indicated that Flo8 is involved in the adhesion and virulence of C. glabrata, with FLO8 deletion leading to decreased expression of EPA1, EPA6, and EPA7 and decreased biofilm formation, hydrophobicity, adhesion, and virulence.

摘要

背景

光滑念珠菌不会发展成致病性假菌丝体;然而,它已成为人类真菌感染的第二大常见病原体,部分原因是其黏附能力和毒力。

目的

本研究旨在确定转录因子 Flo8 是否在白念珠菌的毒力和耐药性中发挥重要作用,在光滑念珠菌中是否也具有相似的作用。

方法

我们构建了光滑念珠菌标准株和 8 株来自不同来源的临床株的 FLO8 缺失株和 FLO8 互补株,并进行了实时定量 PCR、生物膜形成试验、疏水性试验、黏附试验、秀丽隐杆线虫存活试验和药敏试验。

结果

与野生型菌株相比,FLO8 缺失株的生物膜形成、疏水性、黏附性和毒力降低,同时 EPA1、EPA6 和 EPA7 的表达也降低。另一方面,它在抗真菌药物耐药性方面没有变化,尽管 FLO8 删除后 CDR1、CDR2 和 SNQ2 的表达水平增加。

结论

这些结果表明,Flo8 参与了光滑念珠菌的黏附和毒力,FLO8 缺失导致 EPA1、EPA6 和 EPA7 的表达降低,生物膜形成、疏水性、黏附性和毒力降低。

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FLO8 deletion leads to azole resistance by upregulating CDR1 and CDR2 in Candida albicans.
Res Microbiol. 2019 Sep-Oct;170(6-7):272-279. doi: 10.1016/j.resmic.2019.08.005. Epub 2019 Aug 23.
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Enhanced pyruvate production in Candida glabrata by overexpressing the CgAMD1 gene to improve acid tolerance.
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