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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

Comparison of expression ratios (Log10) for the Candida glabrata Sugar Receptor Repressor (SRR) related genes after the knockout of SNF3. *p < 0.1, **p < 0.05, ***p < 0.01.
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Figure 8: Comparison of expression ratios (Log10) for the Candida glabrata Sugar Receptor Repressor (SRR) related genes after the knockout of SNF3. *p < 0.1, **p < 0.05, ***p < 0.01.

Mentions: There are 11 hexose transporters found in C. glabrata. The expressions of these hexose transporters were examined and compared between wild type and SNF3Δ strain. Out of 11 hexose transporters, only nine hexose transporters were studied because the nucleotide sequences of putative hexose transporters CAGL0A02211 and CAGL0A02233 were found to be 96% similar while CAGL0A02662 and CAGL0A02640 displayed 100% similarity. The high similarity among these hexose transporters caused the inability in primer design for the expression study of those genes. Out of nine hexose transporters, six of them were affected with the deletion of SNF3, where four of them (CAGL0A1804_HXT1, CAGL0A01782_HXT4, CAGL0A02211/2233_HXT6/7, and CAGL0D02662/2640_HXT2/10) were down regulated while two (CAGL0A02321_HXT3 and CAGL0A01826_HXT5) were up regulated (Figure 7). In addition, deletion of SNF3 resulted in down-regulation of STD1, YCK1, and YCK2, which serve as the downstream messengers of SNF3 to modulate the expression of hexose transporters (Figure 8). Nevertheless, the expression of RGT2 was up regulated while expression of RGT1, GRR1, and MIG1 did not change significantly with the deletion of SNF3 (Figure 8). These observations suggest the significant role of SNF3 in regulating the signaling pathway of glucose uptake mechanism.


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)

Comparison of expression ratios (Log10) for the Candida glabrata Sugar Receptor Repressor (SRR) related genes after the knockout of SNF3. *p < 0.1, **p < 0.05, ***p < 0.01.
© Copyright Policy
Related In: Results  -  Collection

License
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getmorefigures.php?uid=PMC4664639&req=5

Figure 8: Comparison of expression ratios (Log10) for the Candida glabrata Sugar Receptor Repressor (SRR) related genes after the knockout of SNF3. *p < 0.1, **p < 0.05, ***p < 0.01.
Mentions: There are 11 hexose transporters found in C. glabrata. The expressions of these hexose transporters were examined and compared between wild type and SNF3Δ strain. Out of 11 hexose transporters, only nine hexose transporters were studied because the nucleotide sequences of putative hexose transporters CAGL0A02211 and CAGL0A02233 were found to be 96% similar while CAGL0A02662 and CAGL0A02640 displayed 100% similarity. The high similarity among these hexose transporters caused the inability in primer design for the expression study of those genes. Out of nine hexose transporters, six of them were affected with the deletion of SNF3, where four of them (CAGL0A1804_HXT1, CAGL0A01782_HXT4, CAGL0A02211/2233_HXT6/7, and CAGL0D02662/2640_HXT2/10) were down regulated while two (CAGL0A02321_HXT3 and CAGL0A01826_HXT5) were up regulated (Figure 7). In addition, deletion of SNF3 resulted in down-regulation of STD1, YCK1, and YCK2, which serve as the downstream messengers of SNF3 to modulate the expression of hexose transporters (Figure 8). Nevertheless, the expression of RGT2 was up regulated while expression of RGT1, GRR1, and MIG1 did not change significantly with the deletion of SNF3 (Figure 8). These observations suggest the significant role of SNF3 in regulating the signaling pathway of glucose uptake mechanism.

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