Dataset Information

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

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.

SUBMITTER: Zhao JT

PROVIDER: S-EPMC9151949 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Publications

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

Zhao Jun-Tao JT Chen Ke-Zhi KZ Liu Jin-Yan JY Li Wei-Hua WH Wang Yu-Zhu YZ Wang Lu-Ling LL Xiang Ming-Jie MJ

Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] 20220205 2

<h4>Background</h4>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.<h4>Objectives</h4>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.<h4>Methods</h4>We constructed FLO8 null strains of a C. g ...[more]

PMID: 35122657

Similar Datasets

Project description:IntroductionCandida glabrata has emerged as a fungal pathogen with high infection and mortality rates, and its primary virulence factors are related to adhesion and biofilm formation. These virulence factors in C.glabrata are primarily mediated by epithelial adhesins (Epas), most of which are encoded in subtelomeric regions and regulated by subtelomeric silencing mechanisms. The transcription factor Mss11, known for its regulatory role in adhesion, biofilm formation, and filamentous growth in Saccharomyces cerevisiae and Candida albicans, has also been implicated in the expression of EPA6, suggesting its potential influence on C.glabrata virulence. The present study aims to determine the regulatory role of Mss11 in the virulence of C. glabrata.MethodsIn this work, a Δmss11 null mutant and its complemented strain were constructed from a C.glabrata standard strain. The impact of the transcription factor Mss11 on the virulence of C.glabrata was investigated through a series of phenotypic experiments, including the microbial adhesion to hydrocarbons (MATH) test, adherence assay, biofilm assay, scanning electron microscopy and Galleria mellonella virulence assay. Furthermore, transcriptome sequencing, quantitative reverse transcription polymerase chain reaction (RT-qPCR), and chromatin immunoprecipitation sequencing (ChIP-seq) were employed to investigate the molecular mechanisms behind the regulation of Mss11.ResultsIn C.glabrata, the loss of MSS11 led to a significant reduction in several virulence factors including cell surface hydrophobicity, epithelial cell adhesion, and biofilm formation. These observations were consistent with the decreased virulence of the Δmss11 mutant observed in the Galleria mellonella infection model. Further exploration demonstrated that Mss11 modulates C. glabrata virulence by regulating EPA1 and EPA6 expression. It binds to the upstream regions of EPA1 and EPA6, as well as the promoter regions of the subtelomeric silencing-related genes SIR4, RIF1, and RAP1, indicating the dual regulatory role of Mss11.ConclusionMss11 plays a crucial role in C. glabrata adhesion and biofilm formation, and thus has a broad influence on virulence. This regulation is achieved by regulating the expression of EPA1 and EPA6 through both promoter-specific regulation and subtelomeric silencing.

Dataset Information

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

Background

Objectives

Methods

Results

Conclusions

Publications

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

Similar Datasets

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