Transcriptomics Analysis of Candida albicans Treated with Huanglian Jiedu Decoction Using RNA-seq.

Qianqian Yang,Maocan Tao,Xiaohong Yang,Zhe Chen,Lei Gao,Yi Cao

doi:10.1155/2016/3198249

Abstract

Candida albicans is the major invasive fungal pathogen of humans, causing diseases ranging from superficial mucosal infections to disseminated, systemic infections that are often life-threatening. Resistance of C. albicans to antifungal agents and limited antifungal agents has potentially serious implications for management of infections. As a famous multiherb prescription in China, Huanglian Jiedu Decoction (HLJJD, Orengedokuto in Japan) is efficient against Trichophyton mentagrophytes and C. albicans. But the antifungal mechanism of HLJDD remains unclear. In this study, by using RNA-seq technique, we performed a transcriptomics analysis of gene expression changes for C. albicans under the treatment of HLJDD. A total of 6057 predicted protein-encoding genes were identified. By gene expression analysis, we obtained a total of 735 differentially expressed genes (DEGs), including 700 upregulated genes and 35 downregulated genes. Genes encoding multidrug transporters such as ABC transporter and MFS transporter were identified to be significantly upregulated. Meanwhile, by pathway enrichment analysis, we identified 26 significant pathways, in which pathways of DNA replication and transporter activity were mainly involved. These results might provide insights for the inhibition mechanism of HLJDD against C. albicans.

Highlights

Candida albicans is the most prevalent opportunistic fungal pathogen implicated in superficial mucosal infections as well as invasive disseminated infections, especially in immunocompromised patients [1, 2]
Our preliminary work showed that HLJDD is efficient against Trichophyton mentagrophytes and C. albicans [35]
Expression of 23 genes involved in sterol biosynthesis was detected in the RNA-seq analysis, and expression of 8 genes showed a more than 2-fold increase after the fungus was treated with HLJDD, only the genes encoding sterol 24-C-methyltransferase (ERG6) and C8 sterol isomerase (ERG2) were upregulated by more than 3 times (Table 3). None of these 23 genes was downregulated significantly (Probability > 0.8) by HLJJD. These results indicate that HLJDD might affect sterol biosynthesis of C. albicans

Summary

Introduction

Candida albicans is the most prevalent opportunistic fungal pathogen implicated in superficial mucosal infections as well as invasive disseminated infections, especially in immunocompromised patients [1, 2]. C. albicans infections are usually treated with antifungal agents, such as azoles, echinocandins, and polyene drugs. Limited by the number of available antifungal targets, the antifungal agents still remain restricted. The azoles are the most widely used drugs for treating pathogenic fungal infections. Sterol 14α-demethylase (ERG11) is an ancestral activity of the cytochrome P450 superfamily, which is required for ergosterol biosynthesis in fungi and cholesterol biosynthesis in mammals [3]. As a key enzyme of sterol biosynthesis, Erg is the main target for therapeutic azole antifungal drugs [4, 5]

Methods

Discussion

Conclusion