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

Ng TS, Chew SY, Rangasamy P, Mohd Desa MN, Sandai D, Chong PP, Than LT - Front Microbiol (2015)

Bottom Line: 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.The deletion of SNF3 also resulted in the down-regulation of about half of hexose transporters genes (four out of nine).

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Microbiology and Parasitology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia Serdang, Malaysia.

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.

No MeSH data available.


Related in: MedlinePlus

Survivability of Candida glabrata BG2 and SNF3Δ strains under treatment of three different concentrations of amphotericin B in 0.1% glucose. Unpaired T-test was carried out for the statistical analysis to examine the significant differences (indicated by *) between BG2 and SNF3Δ (p-value < 0.01).
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Figure 5: Survivability of Candida glabrata BG2 and SNF3Δ strains under treatment of three different concentrations of amphotericin B in 0.1% glucose. Unpaired T-test was carried out for the statistical analysis to examine the significant differences (indicated by *) between BG2 and SNF3Δ (p-value < 0.01).

Mentions: Previous study demonstrated the ability of Candida species to withstand antifungal is affected by the type of carbon sources and levels (Ene et al., 2012; Mota et al., 2015; Ng et al., 2015b). With the aim to elucidate further the possible role of SNF3 in regulating the fitness of C. glabrata, the ability of both strains to withstand amphotericin B in low glucose environment was tested. However, the complete retarded growth of SNF3Δ in 0.01% glucose leads to the inability in the effort to set up an unstressed control for the calculation of survival percentage. Thus, only 0.1% glucose was tested in this assay. The growth of both wild type and SNF3Δ strain were arrested at 2 μg/mL of amphotericin B. The wild type strain was able to resist amphotericin B at 1 μg/mL while complete inhibition was observed in the SNF3Δ strain (p-value < 0.01). The wild type showed a better growth in comparison to SNF3Δ strain at 0.5 μg/mL amphotericin B (Figure 5). These data established the fact that glucose sensing by the SNF3 gene may contribute to the ability of C. glabrata in withstanding the effects of amphotericin B under low glucose environment.


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

Ng TS, Chew SY, Rangasamy P, Mohd Desa MN, Sandai D, Chong PP, Than LT - Front Microbiol (2015)

Survivability of Candida glabrata BG2 and SNF3Δ strains under treatment of three different concentrations of amphotericin B in 0.1% glucose. Unpaired T-test was carried out for the statistical analysis to examine the significant differences (indicated by *) between BG2 and SNF3Δ (p-value < 0.01).
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4664639&req=5

Figure 5: Survivability of Candida glabrata BG2 and SNF3Δ strains under treatment of three different concentrations of amphotericin B in 0.1% glucose. Unpaired T-test was carried out for the statistical analysis to examine the significant differences (indicated by *) between BG2 and SNF3Δ (p-value < 0.01).
Mentions: Previous study demonstrated the ability of Candida species to withstand antifungal is affected by the type of carbon sources and levels (Ene et al., 2012; Mota et al., 2015; Ng et al., 2015b). With the aim to elucidate further the possible role of SNF3 in regulating the fitness of C. glabrata, the ability of both strains to withstand amphotericin B in low glucose environment was tested. However, the complete retarded growth of SNF3Δ in 0.01% glucose leads to the inability in the effort to set up an unstressed control for the calculation of survival percentage. Thus, only 0.1% glucose was tested in this assay. The growth of both wild type and SNF3Δ strain were arrested at 2 μg/mL of amphotericin B. The wild type strain was able to resist amphotericin B at 1 μg/mL while complete inhibition was observed in the SNF3Δ strain (p-value < 0.01). The wild type showed a better growth in comparison to SNF3Δ strain at 0.5 μg/mL amphotericin B (Figure 5). These data established the fact that glucose sensing by the SNF3 gene may contribute to the ability of C. glabrata in withstanding the effects of amphotericin B under low glucose environment.

Bottom Line: 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.The deletion of SNF3 also resulted in the down-regulation of about half of hexose transporters genes (four out of nine).

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Microbiology and Parasitology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia Serdang, Malaysia.

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.

No MeSH data available.


Related in: MedlinePlus