Supplementary Table 2: Genes upregulated by the cAMP-signaling pathway during normal budding growth WT/ pde2/ pde2/ Grouping ORF6. ORF19. cap1 cap1 Function
O-acetylhomoserine O-acetylserine sulfhydrylase; involved in sulfur amino acid biosynthesis; immunogenic; Hog1p; biofilm;
Predicted ORF from Assembly 19; Gcn4p-regulatedProtein abundance is affected by URA3 expression in the CAI-4
strain background; alkaline upregulated; Gcn4p-regulatedProtein described as aspartate aminotransferase; soluble protein in
hyphae; alkaline upregulated; amphotericin B repressed
Malic enzyme, mitochondrial protein; transcription regulated by Mig1p and Tup1p; shows colony morphology-related gene
Predicted ORF from Assembly 19; Gcn4p-regulated
Large subunit of heterodimeric alpha-aminoadipate reductase; enzyme of lysine biosynthesis; contains predicted binding sites for AMP and alpha-aminoadipate; feedback inhibited by lysine or
Putative NAD-specific glutamate dehydrogenase; fungal-specific (no human or murine homolog); transcription is regulated by
Nrg1p, Mig1p, Tup1p, and Gcn4pSimilar to an aldose 1-epimerase-related protein; antigenic during
murine systemic infectionSimilar to an aldose 1-epimerase-related protein; antigenic during
Protein described as a putative precursor of a hypha surface antigen; putative GPI-anchor; induced by ciclopirox olamine, ketoconazole, or by Rim101p at pH 8; regulated during planktonic
growth; induced during cell wall regeneration
GPI-anchored cell wall protein; has CRoW motif; not required for filamentous growth; expression is regulated by Rfg1p, Rim101p; repressed by Sfu1p, Hog1p, Tup1p; induced by serum, iron,
alkaline pH, ketoconazole, or ciclopirox olamine
Major cell-surface ferric reductase under low-iron conditions; 7 transmembrane regions and a secretion signal predicted; repressed by Tup1p, Rim101p, Ssn6p, Hog1p, caspofungin;
ciclopirox olamine induced; not required for filamentous growth
Putative GPI-anchored protein that localizes to the cell wall; transcription is decreased upon yeast-hypha switch;
transcriptionally regulated by iron; expression greater in high iron
Surface antigen on elongating hyphae and buds; no obvious hypha defects in mutant; strain variation in number of repeat domains; upregulated in filaments; alkaline upregulated by Rim101p;
13.33 ciclopirox induced; Efg1p- and Cph1p-regulated
Predicted ORF from Assembly 19; flucytosine inducedPredicted ORF from Assembly 19; ketoconazole-induced;
Ergosterol Biosynthesis and Lipid Metabolism ERG251 (XJP2)
Ergosterol Biosynthesis and Lipid Metabolism
Predicted ORF in Assemblies 19 and 20Protein similar to S. cerevisiae Eht1p; transcription is induced in
Ergosterol Biosynthesis and Lipid Metabolism
response to alpha pheromone in Spider medium
Protein similar to pyruvate decarboxylase; antigenic; at cell surface of hypha, but not yeast-form cells; soluble in hyphae; regulated by Gcn4p, Efg1p, Efh1p; fluconazole-induced; repressed
upon amino acid starvation; biofilm-induced
Putative alcohol dehydrogenase; soluble protein in hyphae; fungal-specific (no human or murine homolog); expression is regulated
upon white-opaque switching; regulated by Ssn6pPutative pyruvate decarboxylase; fungal-specific (no human or
Putative pyruvate carboxylase, binds to biotin cofactor; gene is up-regulated in a mutant lacking the Ssk1p response regulator protein, upon benomyl treatment, or in an azole-resistant strain
Putative bHLH (basic region, helix-loop-helix) transcription factor; hypha regulated via Cph1p, Cyr1p; flucytosine, Hog1p induced; amphotericin B, caspofungin repressed; downregulated in azole-
Protein described as hexokinase II; antigenic in human; downregulated in the presence of human neutrophils; regulated by Efg1p; fluconazole-induced; shows colony morphology-related
Alpha subunit of phosphofructokinase (PFK), which is Pfk1p, Pfk2p heteromultimer; PFK is activated by fructose 2,6-bisphosphate or AMP, inhibited by ATP; activity reduced on hypha induction;
phagocytosis-downregulated; fluconazole-induced
Protein described as phosphoglycerate mutase; enzyme of glycolysis; antigenic during murine, human infection; biofilm-, fluconazole-, or amino acid starvation (3-aminotriazole treatment)
Putative ortholog of S. cerevisiae Tpi1p, which is triose-phosphate isomerase involved in glycolysis and gluconeogenesis; antigenic in mouse or human; transposon mutation affects filamentous growth;
Predicted ORF in Assemblies 19 and 20Predicted ORF in Assemblies 19 and 20; possibly spurious ORF
Predicted ORF from Assembly 19; removed from Assembly 20
Predicted ORF in Assemblies 19 and 20Transcription is positively regulated by Sfu1p; possibly spurious
ORF (Annotation Working Group prediction)Predicted ORF from Assembly 19; merged with orf19.3117 in
Predicted ORF from Assembly 19; removed from Assembly 20
Inositol-1-phosphate synthase; enzyme of inositol biosynthesis; antigenic in human; repressed by farnesol (in biofilm) or caspofungin; regulated during planktonic growth; upstream
inositol/choline regulatory element; glycosylation predicted
Iron utilization protein; similar to an S. cerevisiae oxidoreductase, Ynr060wp; regulated by Sfu1p, Nrg1p, Tup1p; alkaline (via Rim101p, low iron, fluphenazine, ciclopirox olamine, flucytosine,
induced; caspofungin, amphotericin B repressed
Similar to GTPase regulators; transcriptionally regulated by iron; expression greater in low iron; possibly spurious ORF (Annotation
Similar to multicopper ferroxidase; transcriptionally regulated by iron; expression greater in low iron; transcription is negatively
regulated by Sfu1p; merged with orf19.4215 in Assembly 20
Protein similar to ferric reductases; transcription is positively regulated by Rim101p; expression greater in low iron; fluconazole-downregulated; ciclopirox olamine induced; colony morphology-
Protein described as a similar to F1 beta subunit of F1F0 ATPase complex; antigenic in human; transcription upregulated in response to ciclopirox olamine; flucytosine induced; caspofungin
repressed; macrophage/pseudohypha-induced
Protein not essential for viability; similar to S. cerevisiae Aah1p, which is an adenine deaminase involved in purine salvage and nitrogen catabolism; shows colony morphology-related gene
regulation by Ssn6p; Hog1p-, biofilm-induced
Similar to oxidoreductases and to S. cerevisiae Yjr096wp; transcription is negatively regulated by Sfu1p; increased transcription is observed upon benomyl treatment; decreased
expression observed in an ssr1 homozygous null mutant
Predicted ORF in Assemblies 19 and 20Predicted ORF from Assembly 19; transcription is regulated by
Protein with similarity to proteasomal 26S regulatory subunit of S. cerevisiae, H. sapiens, Methanobacterium thermoautotrophicum
Protein described as an aminopeptidase; transcription is positively regulated by Sfu1p; transcription is repressed in response to alpha
pheromone in Spider mediumPredicted ORF from Assembly 19; soluble protein in hyphae;
Putative gypsy-like reverse transcriptase; transcription is downregulated in response to treatment with ciclopirox olamine;
3,4-Dihydroxy-2-butanone 4-phosphate synthase; homodimeric enzyme of riboflavin biosynthesis; converts ribulose 5-phosphate to L-3,4-dihydroxy-2-butanone 4-phosphate; transcription
regulated on yeast-hypha switch; macrophage interaction
Inositol phosphoryl transferase, involved in sphingolipid biosynthesis; catalyzes the synthesis of the most abundant sphingolipid, mannose-(inositol-P)2-ceramide, M(IP)2C, from
MIPC; required for wild-type membrane localization of Cdr1p
Protein described as 4-nitrophenyl phosphatase; hypha downregulated; induced in core stress response; induced by heavy
Copper- and zinc-containing superoxide dismutase, expression is regulated during white-opaque switching; ciclopirox olamine induced; caspofungin repressed; member of a gene family that
includes SOD1, SOD4, SOD5, and SOD6Predicted ORF in Assemblies 19 and 20; induced by nitric oxide in
Protein of TSA/alkyl hydroperoxide peroxidase C (AhPC) family; similar to thiol-dependent peroxidases, roles in oxidative stress signaling; immunogenic; on hypha surface, nucleus; yeast-form
nucleus, cytoplasm; neutrophil, peroxide induced
D-Arabinono-1,4-lactone oxidase, involved in biosynthesis of D-erythroascorbic acid, which has a protective role against oxidative damage; required for full virulence in a mouse model of systemic
Similar to thioredoxin; increased transcription is observed upon benomyl treatment; flucytosine induced; amphotericin B repressed; caspofungin repressed; peroxide-induced; upregulated
SUMO, small ubiquitin-like protein; Smt3p-conjugated proteins localize to septation site and mother side of bud neck; C. albicans septins appear not to be Smt3p-modified, in contrast to S. cerevisiae septins; similar to S. cerevisiae Smt3p
Protein described as beta subunit of succinate-CoA ligase; transcription regulated by Mig1p and Tup1p; transcriptionally regulated by iron; expression greater in high iron; merged with
orf19.1860 in Assembly 20Protein described as isocitrate dehydrogenase; transcriptionally
induced by interaction with macrophage; alkaline upregulated
Putative transcription factor; zinc finger; similar to S. cerevisiae Crz1p; homozygous crz1, not crz2, null mutation suppresses fluconazole resistance of homozygous cka2 null (defective in CK2
Protein similar to S. cerevisiae Pob3p, which is involved in chromatin assembly and disassembly; transposon mutation affects
Predicted ORF from Assembly 19; caspofungin repressed
Putative transporter; slightly similar to the Sit1p siderophore transporter; Gcn4p-regulated; fungal-specific (no human or
murine homolog)Putative low-affinity phosphate transporter; fungal-specific (no
Putative potassium transporter; similar to Schwanniomyces occidentalis Hak1p; amphotericin B induced; transcriptionally
induced upon phagocytosis by macrophagePutative sperimidine transporter; fungal-specific (no human or
Putative glucose transporter, major facilitator superfamily; glucose-, fluconazole-, Snf3p-induced, expressed at high glucose; upregulated in biofilm; C. albicans glucose transporter family
comprises 20 members; 12 TM regions predicted
Protein not essential for viability; similar to S. cerevisiae Smf1p, which is a manganese transporter; Gcn4p-regulated; alkaline
Oligopeptide transporter; transports 3-to-5-residue peptides; alleles are distinct, one has intron; not ABC or PTR type transporter; suppresses S. cerevisiae ptr2-2 mutant defects;
induced by BSA or peptides; Stp3p, Hog1p regulated
Predicted ORF in Assemblies 19 and 20; Gcn4p-regulated; flucytosine induced; ketoconazole-repressed; oxidative stress-
Protein described as predicted zinc transporter; ciclopirox olamine, fluconazole, or alkaline downregulated; transcriptionally induced
by interaction with macrophage; amphotericin B inducedAlkaline downregulated; amphotericin B induced; shows colony
morphology-related gene regulation by Ssn6pPutative general amino acid permease; Plc1p-regulated; Gcn4p-
regulated; fungal-specific (no human or murine homolog)
Putative oligopeptide transporter; regulated by Stp2p and Stp3p; transcriptionally induced upon phagocytosis by macrophage;
downregulated by Rim101p at pH 8Predicted ORF in Assemblies 19 and 20; regulated by Tsa1p,
Transcriptionally regulated by iron or by yeast-hypha switch; expression greater in high iron, decreased upon yeast-hypha switch; downregulation correlates with clinical development of
fluconazole resistance; Ras1p-regulatedPredicted ORF in Assemblies 19 and 20; ciclopirox olamine
induced; regulated by Ssn6p; induced by nitric oxide in yhb1 Predicted ORF in Assemblies 19 and 20; decreased expression
observed in an ssr1 homozygous null mutant
Predicted ORF in Assemblies 19 and 20; ketoconazole-repressed
Predicted membrane protein; similar to S. cerevisiae Ynr018wp
Protein not essential for viability; similar to S. cerevisiae Ecm21p (may have cell wall role); alkaline upregulated by Rim101p; fluconazole induced; caspofungin repressed; downregulated in
azole-resistant strain overexpressing MDR1
Putative 3-phosphoserine phosphatase; fungal-specific (no human or murine homolog); increased transcription is observed upon
benomyl treatment or in an azole-resistant strain that Predicted ORF in Assemblies 19 and 20; downregulation correlates
with clinical development of fluconazole resistance
Protein similar to S. cerevisiae Sha3p, which is a serine/threonine kinase involved in glucose transport; transposon mutation affects filamentous growth; fluconazole-induced; ketoconazole-repressed;
induced in response to alpha pheromoneProtein described as having a role in Ty3 transposition; decreased
expression in hyphae compared to yeast-form cells
Putative cell wall protein; transcription is negatively regulated by Rim101p, Efg1p, Ssn6p; alkaline downregulated; predicted signal
Predicted ORF in Assemblies 19 and 20; decreased transcription is observed upon fluphenazine treatment or in an azole-resistant
strain that overexpresses CDR1 and CDR2Predicted ORF in Assemblies 19 and 20; fluconazole-induced;
Topical metformin inhibits chloride secretion but not sodium absorption across human nasal epithelium Maulik Shah, Vinothan Ganesaratnam, Deborah Baines, Emma Baker Division of Biomedical Sciences, St George's, University of London, United Kingdom Background: In cystic fibrosis (CF), mutations of the cystic fibrosis transmembrane regulator (CFTR) lead to reduced chloride secretion and i
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