The evolutionary rewiring of ubiquitination targets has reprogrammed the regulation of carbon assimilation in the pathogenic yeast Candida albicans

Doblin Sandai, Zhikang Yin, Laura Selway, David Stead, Janet Walker, Michelle D. Leach, Iryna Bohovych, Iuliana V. Ene, Stavroula Kastora, Susan Budge, Carol A. Munro, Frank C. Odds, Neil A. R. Gow, Alistair J. P. Brown

Research output: Contribution to journalArticle

48 Citations (Scopus)
4 Downloads (Pure)

Abstract

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.
Original languageEnglish
Article numbere00495-12
Number of pages12
JournalmBio
Volume3
Issue number6
DOIs
Publication statusPublished - 11 Dec 2012

Fingerprint

Ubiquitination
Candida albicans
Carbon
Yeasts
Saccharomyces cerevisiae
Glucose
Isocitrate Lyase
Phosphoenolpyruvate
Enzymes
Proteome
Ubiquitin
Carboxylic Acids
Metabolic Networks and Pathways
Transcriptome
Fatty Acids
Food

Cite this

The evolutionary rewiring of ubiquitination targets has reprogrammed the regulation of carbon assimilation in the pathogenic yeast Candida albicans. / Sandai, Doblin; Yin, Zhikang; Selway, Laura; Stead, David ; Walker, Janet; Leach, Michelle D.; Bohovych, Iryna ; Ene, Iuliana V. ; Kastora, Stavroula; Budge, Susan; Munro, Carol A.; Odds, Frank C. ; Gow, Neil A. R.; Brown, Alistair J. P. .

In: mBio, Vol. 3, No. 6, e00495-12, 11.12.2012.

Research output: Contribution to journalArticle

Sandai, Doblin ; Yin, Zhikang ; Selway, Laura ; Stead, David ; Walker, Janet ; Leach, Michelle D. ; Bohovych, Iryna ; Ene, Iuliana V. ; Kastora, Stavroula ; Budge, Susan ; Munro, Carol A. ; Odds, Frank C. ; Gow, Neil A. R. ; Brown, Alistair J. P. . / The evolutionary rewiring of ubiquitination targets has reprogrammed the regulation of carbon assimilation in the pathogenic yeast Candida albicans. In: mBio. 2012 ; Vol. 3, No. 6.
@article{3ccafbceb70d4e138e30134883274804,
title = "The evolutionary rewiring of ubiquitination targets has reprogrammed the regulation of carbon assimilation in the pathogenic yeast Candida albicans",
abstract = "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.",
author = "Doblin Sandai and Zhikang Yin and Laura Selway and David Stead and Janet Walker and Leach, {Michelle D.} and Iryna Bohovych and Ene, {Iuliana V.} and Stavroula Kastora and Susan Budge and Munro, {Carol A.} and Odds, {Frank C.} and Gow, {Neil A. R.} and Brown, {Alistair J. P.}",
note = "Date of Acceptance: 13/11/2012 This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-ShareAlike 3.0 Unported license, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited. Correction for Sandai et al., The Evolutionary Rewiring of Ubiquitination Targets Has Reprogrammed the Regulation of Carbon Assimilation in the Pathogenic Yeast Candida albicans published 20-01-2015 DOI: 10.1128/mBio.02489-14",
year = "2012",
month = "12",
day = "11",
doi = "10.1128/mBio.00495-12",
language = "English",
volume = "3",
journal = "mBio",
issn = "2161-2129",
publisher = "American Society for Microbiology",
number = "6",

}

TY - JOUR

T1 - The evolutionary rewiring of ubiquitination targets has reprogrammed the regulation of carbon assimilation in the pathogenic yeast Candida albicans

AU - Sandai, Doblin

AU - Yin, Zhikang

AU - Selway, Laura

AU - Stead, David

AU - Walker, Janet

AU - Leach, Michelle D.

AU - Bohovych, Iryna

AU - Ene, Iuliana V.

AU - Kastora, Stavroula

AU - Budge, Susan

AU - Munro, Carol A.

AU - Odds, Frank C.

AU - Gow, Neil A. R.

AU - Brown, Alistair J. P.

N1 - Date of Acceptance: 13/11/2012 This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-ShareAlike 3.0 Unported license, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited. Correction for Sandai et al., The Evolutionary Rewiring of Ubiquitination Targets Has Reprogrammed the Regulation of Carbon Assimilation in the Pathogenic Yeast Candida albicans published 20-01-2015 DOI: 10.1128/mBio.02489-14

PY - 2012/12/11

Y1 - 2012/12/11

N2 - 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.

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.

U2 - 10.1128/mBio.00495-12

DO - 10.1128/mBio.00495-12

M3 - Article

VL - 3

JO - mBio

JF - mBio

SN - 2161-2129

IS - 6

M1 - e00495-12

ER -