SNF3 as High Affinity Glucose Sensor and Its Function in Supporting the Viability of Candida glabrata under Glucose-Limited Environment.

Tzu Shan Ng,Doblin Sandai,Shu Yih Chew,Mohd N Mohd Desa,Leslie Thian Lung Than,Pei Pei Chong,Premmala Rangasamy

doi:10.3389/fmicb.2015.01334

Tzu Shan Ng, Doblin Sandai + Show 5 more

Open Access

https://doi.org/10.3389/fmicb.2015.01334

Copy DOI

Abstract

Candida glabrata is an emerging human fungal pathogen that has efficacious nutrient sensing and responsiveness ability. It can be seen through its ability to thrive in diverse range of nutrient limited-human anatomical sites. Therefore, nutrient sensing particularly glucose sensing is thought to be crucial in contributing to the development and fitness of the pathogen. This study aimed to elucidate the role of SNF3 (Sucrose Non Fermenting 3) as a glucose sensor and its possible role in contributing to the fitness and survivability of C. glabrata in glucose-limited environment. The SNF3 knockout strain was constructed and subjected to different glucose concentrations to evaluate its growth, biofilm formation, amphotericin B susceptibility, ex vivo survivability and effects on the transcriptional profiling of the sugar receptor repressor (SRR) pathway-related genes. The CgSNF3Δ strain showed a retarded growth in low glucose environments (0.01 and 0.1%) in both fermentation and respiration-preferred conditions but grew well in high glucose concentration environments (1 and 2%). It was also found to be more susceptible to amphotericin B in low glucose environment (0.1%) and macrophage engulfment but showed no difference in the biofilm formation capability. The deletion of SNF3 also resulted in the down-regulation of about half of hexose transporters genes (four out of nine). Overall, the deletion of SNF3 causes significant reduction in the ability of C. glabrata to sense limited surrounding glucose and consequently disrupts its competency to transport and perform the uptake of this critical nutrient. This study highlighted the role of SNF3 as a high affinity glucose sensor and its role in aiding the survivability of C. glabrata particularly in glucose limited environment.

Highlights

Glucose is commonly known as an important carbon source and energy for many organisms
SNF3 is deemed to be more important in fermentation process where the growth defect of SNF3 was found to be more severe in fermentation-preferred condition
Data presented in present study is suggestive of the role of SNF3 as high affinity glucose sensor in C. glabrata, which is essential for it to grow in glucose-limited environment

Summary

Introduction

Glucose is commonly known as an important carbon source and energy for many organisms. Brown et al (2006) have demonstrated that the loss of Hgt, a high affinity glucose sensor resulted in a less virulent C. albicans type that failed to grow in low glucose and fermentation-preferred environments. The loss of Hgt affects the ability of C. albicans to perform the yeast-hyphal morphological switch and compromises its pathogenicity in mouse model of disseminated candidiasis (Brown et al, 2006). Apart from that, the ability to transport glucose by Cryptococcus neoformans is diminished with the loss of Hxs, a high affinity glucose sensor-like protein (Liu et al, 2013). The diminished glucose uptake activity leads to an attenuated strain of C. neoformans in which the strain demonstrated a delay in lethal infection in mice model. Little is known about the role of high affinity glucose sensor in the emerging human fungal pathogen, Candida glabrata

Objectives

Methods

Results

Conclusion