Evaluation of global transcriptomic profile of candida glabrata during biofilm and planktonic phase

Abstract

The present study was designed with an aim to decipher differentially expressed genes (DEGs), differential transcript isoform usage (DTU) and metabolic pathways involved in the mature biofilm of Candida glabrata (NCCPF-100037) which may eventually prove to be helpful in identifying the targets for designing anti-fungal therapeutic options. The study was executed using various approaches (transcriptomics, functional genomics and gene deletion) and it revealed that metabolic plasticity of C. glabrata (NCCPF-100037) in biofilm stage modulates its virulence and survival ability to counter the stress and may promote its transition from commensal to opportunistic pathogen. Highthroughput RNA-Seq approach with comprehensive bioinformatics analysis revealed the DEGs, DTE and DTU under the biofilm growth mode of C. glabrata. The current study deciphered the important genes, gene sets and their interactome that could play a pivotal in the biofilm formation. Additionally, the gene deletion approach confirmed the role of PCK1 in alternative carbon source assimilation and PEP1 in protein sorting to counter the nutrient and oxidative stress prevailing in the mature biofilm of C. glabrata (NCPPF-100037). Thus, the study demonstrated that up-regulation of CgICL, CgMLS and CgPCK1 are associated with the glyoxylate cycle and gluconeogenesis pathways. This is a first ever study to highlight the significance of putative proteins encoded by identified genes and transcript isoforms coupled with utilization of specific transcript isoforms under the biofilm growth phase of C. glabrata. The observations deduced from the present study along with future work on characterization of the proteins involved in this intricate process may prove to be beneficial for designing novel antifungal strategies. newline