Metabolic adaptation via regulated enzyme degradation in the pathogenic yeast Candida albicans
The virulence of Candida albicans is dependent upon fitness attributes as well as virulence factors. These attributes include robust stress responses and metabolic flexibility. The assimilation of carbon sources is important for growth and essential for the establishment of infections by C. albicans...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier Masson
2017
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| Online Access: | http://psasir.upm.edu.my/id/eprint/62396/1/Metabolic%20adaptation%20via%20regulated%20enzyme%20degradation%20in%20the%20pathogenic%20yeast%20Candida%20albicans.pdf |
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| author | Ting, Seng Yeat Ishola, Oluwaseun Ayodeji Ahmed, M. A. Tabana, Yasser Mahfooth Tabana Dahham, Saad Sabbar Agha, Mohamad Taleb Musa, S. F. Muhammed, R. Than, Leslie Thian Lung Sandai, Doblin |
| author_facet | Ting, Seng Yeat Ishola, Oluwaseun Ayodeji Ahmed, M. A. Tabana, Yasser Mahfooth Tabana Dahham, Saad Sabbar Agha, Mohamad Taleb Musa, S. F. Muhammed, R. Than, Leslie Thian Lung Sandai, Doblin |
| author_sort | Ting, Seng Yeat |
| collection | UPM |
| description | The virulence of Candida albicans is dependent upon fitness attributes as well as virulence factors. These attributes include robust stress responses and metabolic flexibility. The assimilation of carbon sources is important for growth and essential for the establishment of infections by C. albicans. Previous studies showed that the C. albicans ICL1 genes, which encode the glyoxylate cycle enzymes isocitratelyase are required for growth on non-fermentable carbon sources such as lactate and oleic acid and were repressed by 2% glucose. In contrast to S. cerevsiae, the enzyme CaIcl1 was not destabilised by glucose, resulting with its metabolite remaining at high levels. Further glucose addition has caused CaIcl1 to lose its signal and mechanisms that trigger destabilization in response to glucose. Another purpose of this study was to test the stability of the Icl1 enzyme in response to the dietary sugars, fructose, and galactose. In the present study, the ICL1 mRNAs expression was quantified using Quantitative Real Time PCR, whereby the stability of protein was measured and quantified using Western blot and phosphoimager, and the replacing and cloning of ICL1 ORF by gene recombination and ubiquitin binding was conducted via co-immuno-precipitation. Following an analogous experimental approach, the analysis was repeated using S. cerevisiaeas a control. Both galactose and fructose were found to trigger the degradation of the ICL1 transcript in C. albicans. The Icl1 enzyme was stable following galactose addition but was degraded in response to fructose. C. albicans Icl1 (CaIcl1) was also subjected to fructose-accelerated degradation when expressed in S. cerevisiae, indicating that, although it lacks a ubiquitination site, CaIcl1 is sensitive to fructose-accelerated protein degradation. The addition of an ubiquitination site to CaIcl1 resulted in this enzyme becoming sensitive to galactose-accelerated degradation and increases its rate of degradation in the presence of fructose. It can be concluded that ubiquitin-independent pathways of fructose-accelerated enzyme degradation exist in C. albicans. |
| first_indexed | 2024-03-06T09:42:44Z |
| format | Article |
| id | upm.eprints-62396 |
| institution | Universiti Putra Malaysia |
| language | English |
| last_indexed | 2024-03-06T09:42:44Z |
| publishDate | 2017 |
| publisher | Elsevier Masson |
| record_format | dspace |
| spelling | upm.eprints-623962020-01-10T05:37:57Z http://psasir.upm.edu.my/id/eprint/62396/ Metabolic adaptation via regulated enzyme degradation in the pathogenic yeast Candida albicans Ting, Seng Yeat Ishola, Oluwaseun Ayodeji Ahmed, M. A. Tabana, Yasser Mahfooth Tabana Dahham, Saad Sabbar Agha, Mohamad Taleb Musa, S. F. Muhammed, R. Than, Leslie Thian Lung Sandai, Doblin The virulence of Candida albicans is dependent upon fitness attributes as well as virulence factors. These attributes include robust stress responses and metabolic flexibility. The assimilation of carbon sources is important for growth and essential for the establishment of infections by C. albicans. Previous studies showed that the C. albicans ICL1 genes, which encode the glyoxylate cycle enzymes isocitratelyase are required for growth on non-fermentable carbon sources such as lactate and oleic acid and were repressed by 2% glucose. In contrast to S. cerevsiae, the enzyme CaIcl1 was not destabilised by glucose, resulting with its metabolite remaining at high levels. Further glucose addition has caused CaIcl1 to lose its signal and mechanisms that trigger destabilization in response to glucose. Another purpose of this study was to test the stability of the Icl1 enzyme in response to the dietary sugars, fructose, and galactose. In the present study, the ICL1 mRNAs expression was quantified using Quantitative Real Time PCR, whereby the stability of protein was measured and quantified using Western blot and phosphoimager, and the replacing and cloning of ICL1 ORF by gene recombination and ubiquitin binding was conducted via co-immuno-precipitation. Following an analogous experimental approach, the analysis was repeated using S. cerevisiaeas a control. Both galactose and fructose were found to trigger the degradation of the ICL1 transcript in C. albicans. The Icl1 enzyme was stable following galactose addition but was degraded in response to fructose. C. albicans Icl1 (CaIcl1) was also subjected to fructose-accelerated degradation when expressed in S. cerevisiae, indicating that, although it lacks a ubiquitination site, CaIcl1 is sensitive to fructose-accelerated protein degradation. The addition of an ubiquitination site to CaIcl1 resulted in this enzyme becoming sensitive to galactose-accelerated degradation and increases its rate of degradation in the presence of fructose. It can be concluded that ubiquitin-independent pathways of fructose-accelerated enzyme degradation exist in C. albicans. Elsevier Masson 2017-03 Article PeerReviewed text en http://psasir.upm.edu.my/id/eprint/62396/1/Metabolic%20adaptation%20via%20regulated%20enzyme%20degradation%20in%20the%20pathogenic%20yeast%20Candida%20albicans.pdf Ting, Seng Yeat and Ishola, Oluwaseun Ayodeji and Ahmed, M. A. and Tabana, Yasser Mahfooth Tabana and Dahham, Saad Sabbar and Agha, Mohamad Taleb and Musa, S. F. and Muhammed, R. and Than, Leslie Thian Lung and Sandai, Doblin (2017) Metabolic adaptation via regulated enzyme degradation in the pathogenic yeast Candida albicans. Journal de Mycologie Medicale, 27 (1). 98 - 108. ISSN 1156-5233; ESSN: 1773-0449 https://www.sciencedirect.com/science/article/pii/S1156523316302773 10.1016/j.mycmed.2016.12.002 |
| spellingShingle | Ting, Seng Yeat Ishola, Oluwaseun Ayodeji Ahmed, M. A. Tabana, Yasser Mahfooth Tabana Dahham, Saad Sabbar Agha, Mohamad Taleb Musa, S. F. Muhammed, R. Than, Leslie Thian Lung Sandai, Doblin Metabolic adaptation via regulated enzyme degradation in the pathogenic yeast Candida albicans |
| title | Metabolic adaptation via regulated enzyme degradation in the pathogenic yeast Candida albicans |
| title_full | Metabolic adaptation via regulated enzyme degradation in the pathogenic yeast Candida albicans |
| title_fullStr | Metabolic adaptation via regulated enzyme degradation in the pathogenic yeast Candida albicans |
| title_full_unstemmed | Metabolic adaptation via regulated enzyme degradation in the pathogenic yeast Candida albicans |
| title_short | Metabolic adaptation via regulated enzyme degradation in the pathogenic yeast Candida albicans |
| title_sort | metabolic adaptation via regulated enzyme degradation in the pathogenic yeast candida albicans |
| url | http://psasir.upm.edu.my/id/eprint/62396/1/Metabolic%20adaptation%20via%20regulated%20enzyme%20degradation%20in%20the%20pathogenic%20yeast%20Candida%20albicans.pdf |
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