PMID- 23232717
OWN - NLM
STAT- MEDLINE
DCOM- 20130403
LR  - 20230612
IS  - 2150-7511 (Electronic)
VI  - 3
IP  - 6
DP  - 2012 Dec 11
TI  - The evolutionary rewiring of ubiquitination targets has reprogrammed the 
      regulation of carbon assimilation in the pathogenic yeast Candida albicans.
LID - 10.1128/mBio.00495-12 [doi]
LID - e00495-12
AB  - Microbes must assimilate carbon to grow and colonize their niches. Transcript 
      profiling has suggested that Candida albicans, a major pathogen of humans, 
      regulates its carbon assimilation in an analogous fashion to the model yeast 
      Saccharomyces cerevisiae, repressing metabolic pathways required for the use of 
      alterative nonpreferred carbon sources when sugars are available. However, we 
      show that there is significant dislocation between the proteome and transcriptome 
      in C. albicans. Glucose triggers the degradation of the ICL1 and PCK1 transcripts 
      in C. albicans, yet isocitrate lyase (Icl1) and phosphoenolpyruvate carboxykinase 
      (Pck1) are stable and are retained. Indeed, numerous enzymes required for the 
      assimilation of carboxylic and fatty acids are not degraded in response to 
      glucose. However, when expressed in C. albicans, S. cerevisiae Icl1 (ScIcl1) is 
      subjected to glucose-accelerated degradation, indicating that like S. cerevisiae, 
      this pathogen has the molecular apparatus required to execute ubiquitin-dependent 
      catabolite inactivation. C. albicans Icl1 (CaIcl1) lacks analogous ubiquitination 
      sites and is stable under these conditions, but the addition of a ubiquitination 
      site programs glucose-accelerated degradation of CaIcl1. Also, catabolite 
      inactivation is slowed in C. albicans ubi4 cells. Ubiquitination sites are 
      present in gluconeogenic and glyoxylate cycle enzymes from S. cerevisiae but 
      absent from their C. albicans homologues. We conclude that evolutionary rewiring 
      of ubiquitination targets has meant that following glucose exposure, C. albicans 
      retains key metabolic functions, allowing it to continue to assimilate 
      alternative carbon sources. This metabolic flexibility may be critical during 
      infection, facilitating the rapid colonization of dynamic host niches containing 
      complex arrays of nutrients. IMPORTANCE Pathogenic microbes must assimilate a 
      range of carbon sources to grow and colonize their hosts. Current views about 
      carbon assimilation in the pathogenic yeast Candida albicans are strongly 
      influenced by the Saccharomyces cerevisiae paradigm in which cells faced with 
      choices of nutrients first use energetically favorable sugars, degrading enzymes 
      required for the assimilation of less favorable alternative carbon sources. We 
      show that this is not the case in C. albicans because there has been significant 
      evolutionary rewiring of the molecular signals that promote enzyme degradation in 
      response to glucose. As a result, this major pathogen of humans retains enzymes 
      required for the utilization of physiologically relevant carbon sources such as 
      lactic acid and fatty acids, allowing it to continue to use these host nutrients 
      even when glucose is available. This phenomenon probably enhances efficient 
      colonization of host niches where sugars are only transiently available.
FAU - Sandai, Doblin
AU  - Sandai D
AD  - School of Medical Sciences, University of Aberdeen, Institute of Medical 
      Sciences, Foresterhill, Aberdeen, United Kingdom.
FAU - Yin, Zhikang
AU  - Yin Z
FAU - Selway, Laura
AU  - Selway L
FAU - Stead, David
AU  - Stead D
FAU - Walker, Janet
AU  - Walker J
FAU - Leach, Michelle D
AU  - Leach MD
FAU - Bohovych, Iryna
AU  - Bohovych I
FAU - Ene, Iuliana V
AU  - Ene IV
FAU - Kastora, Stavroula
AU  - Kastora S
FAU - Budge, Susan
AU  - Budge S
FAU - Munro, Carol A
AU  - Munro CA
FAU - Odds, Frank C
AU  - Odds FC
FAU - Gow, Neil A R
AU  - Gow NA
FAU - Brown, Alistair J P
AU  - Brown AJ
LA  - eng
GR  - 249793/ERC_/European Research Council/International
GR  - R01 GM094198/GM/NIGMS NIH HHS/United States
GR  - BB/D009308/1/BB_/Biotechnology and Biological Sciences Research Council/United 
      Kingdom
GR  - WT_/Wellcome Trust/United Kingdom
GR  - BB/F00513X/1/BB_/Biotechnology and Biological Sciences Research Council/United 
      Kingdom
GR  - BBS/B/06679/BB_/Biotechnology and Biological Sciences Research Council/United 
      Kingdom
GR  - NIH P30 CA068485/CA/NCI NIH HHS/United States
GR  - BB/F000111/1/BB_/Biotechnology and Biological Sciences Research Council/United 
      Kingdom
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20121211
PL  - United States
TA  - mBio
JT  - mBio
JID - 101519231
RN  - 0 (Fungal Proteins)
RN  - 0 (Proteome)
RN  - 7440-44-0 (Carbon)
SB  - IM
CIN - MBio. 2013;4(1):e00034-13. PMID: 23386434
EIN - MBio. 2015;6(1). pii: e02489-14. doi: 10.1128/mBio.02489-14. PMID: 25604791
MH  - Candida albicans/*genetics/*metabolism
MH  - Carbohydrate Metabolism
MH  - Carbon/*metabolism
MH  - Evolution, Molecular
MH  - Fungal Proteins/*metabolism
MH  - *Gene Expression Regulation, Fungal
MH  - Humans
MH  - Lipid Metabolism
MH  - Proteome/analysis
MH  - Transcriptome
MH  - *Ubiquitination
PMC - PMC3520108
EDAT- 2012/12/13 06:00
MHDA- 2013/04/04 06:00
PMCR- 2012/12/11
CRDT- 2012/12/13 06:00
PHST- 2012/12/13 06:00 [entrez]
PHST- 2012/12/13 06:00 [pubmed]
PHST- 2013/04/04 06:00 [medline]
PHST- 2012/12/11 00:00 [pmc-release]
AID - mBio.00495-12 [pii]
AID - mBio00495-12 [pii]
AID - 10.1128/mBio.00495-12 [doi]
PST - epublish
SO  - mBio. 2012 Dec 11;3(6):e00495-12. doi: 10.1128/mBio.00495-12.