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

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.

Sugar Sensing and Signaling in Candida albicans and Candida glabrata

“…This hypothesis is based on recent findings regarding the emergence of antifungal resistance genes and the number of adhesins present in C. glabrata clinical isolates (Vale-Silva et al, 2017; Salazar et al, 2018). The glucose sensor Cg Snf3 was first characterized by the group of Than as the most important and high affinity sensor of environmental glucose concentrations (Ng et al, 2015). Cg Snf3 and Cg Rgt2 are 59 and 60% similar to their orthologs in S. cerevisiae , respectively.…”

“…The sensor is less important for growth on high glucose levels (1–2%) as it is probably not expressed under these conditions. Deletion of Cg SNF3 results in downregulation of four out of nine hexose transporter genes (Ng et al, 2015). Furthermore, the disruption of Cg SNF3 leads to the downregulation of Cg YCK1 , Cg YCK2 , and Cg STD1 .…”

Genotypic and Phenotypic Characterization of Fecal Staphylococcus epidermidis Isolates Suggests Plasticity to Adapt to Different Human Body Sites

“…Twenty milliliter of BHI was inoculated with 1% of each studied strain with or without 0.3% porcine bile and triplicate 300 µl aliquots were transferred to a honeycomb R sterile plate (Thermo Fisher Scientific, United Kingdom) for Bioscreen C (Labsystems Diagnostics Oy, Finland) for measuring aerobic growth [optical density (OD) at 600 nm] and to a 96-well plate for Infinite F50 (Tecan Group, Switzerland) for anaerobic conditions, using Bioscreener and Gen5 Data Analysis as software, respectively. Growth rate (µ) was calculated using the formula µ = 2.303 (log OD 2 − log OD 1 )/t 2 − t 1 (Ng et al, 2015) where OD 2 is the value that doubles OD 1 , and t 2 and t 1 the time at those two measurements.…”

Differential Effects of Varying Concentrations of Phosphorus, Iron, and Nitrogen in N2-Fixing Cyanobacteria

“…of the cells), and this was measured every 2–4 days. Growth rate (μ, day –1 ) and generation time ( T g , days) were calculated following the formula described in Widdel (2010) and Ng et al (2015) :…”