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

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

JOURNAL=Frontiers in Microbiology

VOLUME=6

YEAR=2015

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2015.01334

DOI=10.3389/fmicb.2015.01334

ISSN=1664-302X

ABSTRACT=<p><italic>Candida glabrata</italic> 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 <italic>SNF3</italic> (<underline>S</underline>ucrose <underline>N</underline>on <underline>F</underline>ermenting 3) as a glucose sensor and its possible role in contributing to the fitness and survivability of <italic>C. glabrata</italic> in glucose-limited environment. The <italic>SNF3</italic> knockout strain was constructed and subjected to different glucose concentrations to evaluate its growth, biofilm formation, amphotericin B susceptibility, <italic>ex vivo</italic> survivability and effects on the transcriptional profiling of the sugar receptor repressor (SRR) pathway-related genes. The <italic>CgSNF3</italic>Δ 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 <italic>SNF3</italic> also resulted in the down-regulation of about half of hexose transporters genes (four out of nine). Overall, the deletion of <italic>SNF3</italic> causes significant reduction in the ability of <italic>C. glabrata</italic> 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 <italic>SNF3</italic> as a high affinity glucose sensor and its role in aiding the survivability of <italic>C. glabrata</italic> particularly in glucose limited environment.</p>