PMID- 28041812 OWN - NLM STAT- MEDLINE DCOM- 20171002 LR - 20171002 IS - 1773-0449 (Electronic) IS - 1156-5233 (Linking) VI - 27 IP - 1 DP - 2017 Mar TI - Metabolic adaptation via regulated enzyme degradation in the pathogenic yeast Candida albicans. PG - 98-108 LID - S1156-5233(16)30277-3 [pii] LID - 10.1016/j.mycmed.2016.12.002 [doi] AB - 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. CI - Copyright (c) 2016 Elsevier Masson SAS. All rights reserved. FAU - Ting, S Y AU - Ting SY AD - Infectomics Cluster, advanced medical and dental institute, universiti Sains Malaysia, Jln Tun Hamdan Sheikh Tahir, 13200 Bertam Penang, Malaysia. FAU - Ishola, O A AU - Ishola OA AD - Infectomics Cluster, advanced medical and dental institute, universiti Sains Malaysia, Jln Tun Hamdan Sheikh Tahir, 13200 Bertam Penang, Malaysia. FAU - Ahmed, M A AU - Ahmed MA AD - Infectomics Cluster, advanced medical and dental institute, universiti Sains Malaysia, Jln Tun Hamdan Sheikh Tahir, 13200 Bertam Penang, Malaysia. FAU - Tabana, Y M AU - Tabana YM AD - Infectomics Cluster, advanced medical and dental institute, universiti Sains Malaysia, Jln Tun Hamdan Sheikh Tahir, 13200 Bertam Penang, Malaysia. FAU - Dahham, S AU - Dahham S AD - Infectomics Cluster, advanced medical and dental institute, universiti Sains Malaysia, Jln Tun Hamdan Sheikh Tahir, 13200 Bertam Penang, Malaysia. FAU - Agha, M T AU - Agha MT AD - Infectomics Cluster, advanced medical and dental institute, universiti Sains Malaysia, Jln Tun Hamdan Sheikh Tahir, 13200 Bertam Penang, Malaysia. FAU - Musa, S F AU - Musa SF AD - Infectomics Cluster, advanced medical and dental institute, universiti Sains Malaysia, Jln Tun Hamdan Sheikh Tahir, 13200 Bertam Penang, Malaysia. FAU - Muhammed, R AU - Muhammed R AD - Regenerative medicine cluster, advanced medical and dental institute, UniversitiSains Malaysia, 13200 Bertam Penang, Malaysia. FAU - Than, L T L AU - Than LT AD - Department of medical microbiology and parasitology, faculty of medicine and health sciences, universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia. FAU - Sandai, D AU - Sandai D AD - Infectomics Cluster, advanced medical and dental institute, universiti Sains Malaysia, Jln Tun Hamdan Sheikh Tahir, 13200 Bertam Penang, Malaysia. Electronic address: doblin@usm.my. LA - eng PT - Journal Article DEP - 20161229 PL - France TA - J Mycol Med JT - Journal de mycologie medicale JID - 9425651 RN - 0 (Glyoxylates) RN - 0 (Saccharomyces cerevisiae Proteins) RN - 30237-26-4 (Fructose) RN - EC 4.1.3.1 (ICL1 protein, S cerevisiae) RN - EC 4.1.3.1 (Isocitrate Lyase) RN - JQ39C92HH6 (glyoxylic acid) RN - X2RN3Q8DNE (Galactose) SB - IM MH - Adaptation, Physiological/drug effects MH - Candida albicans/genetics/*metabolism/*pathogenicity MH - Carbohydrate Metabolism/*physiology MH - Fructose/metabolism/pharmacology MH - Galactose/metabolism/pharmacology MH - Glyoxylates/metabolism MH - Isocitrate Lyase/*metabolism MH - *Proteolysis/drug effects MH - Saccharomyces cerevisiae/metabolism MH - Saccharomyces cerevisiae Proteins/metabolism MH - Ubiquitination/drug effects MH - Virulence/*physiology OTO - NOTNLM OT - Acide isocitrique-lyase OT - Adaptation OT - Candida albicans OT - Cycle du glyoxylate OT - Glyoxylate cycle OT - Isocitratelyase OT - Pathogenicity OT - Pathogene OT - Virulence EDAT- 2017/01/04 06:00 MHDA- 2017/10/03 06:00 CRDT- 2017/01/03 06:00 PHST- 2016/06/11 00:00 [received] PHST- 2016/11/01 00:00 [revised] PHST- 2016/12/05 00:00 [accepted] PHST- 2017/01/04 06:00 [pubmed] PHST- 2017/10/03 06:00 [medline] PHST- 2017/01/03 06:00 [entrez] AID - S1156-5233(16)30277-3 [pii] AID - 10.1016/j.mycmed.2016.12.002 [doi] PST - ppublish SO - J Mycol Med. 2017 Mar;27(1):98-108. doi: 10.1016/j.mycmed.2016.12.002. Epub 2016 Dec 29.