TABLE 2.

Genes differentially expressed in wild-type C. glabrata cells challenged with fluconazole^a

Functional group	C. glabrata gene	Description	Log2-fold change
			WT FLC/WT control	Δcgrpn4 FLC/WT FLC
Drug resistance	CDR1	Multidrug transporter of the ABC superfamily, involved in resistance to azoles; expression regulated by Pdr1p; increased abundance in azole-resistant strains; expression increased by loss of the mitochondrial genome	0.81	0.42
Sterol metabolism	ERG1b	Squalene epoxidase with role in ergosterol synthesis; involved in growth under conditions of low oxygen tension	0.83	−0.61
	ERG2b	C-8 sterol isomerase	1.10	−0.71
	ERG3b	Delta-5,6-sterol desaturase; C-5 sterol desaturase; predicted transmembrane domain and endoplasmic reticulum binding motif; gene used for molecular typing of C. glabrata strain isolates	1.07	−0.63
	ERG4	Putative C-24 sterol reductase	0.83	−0.46
	ERG5	Putative C-22 sterol desaturase	0.58	−0.24
	ERG6	C-24 sterol methyltransferase; mutation confers resistance to amphotericin B and nystatin and increased sensitivity to azoles	0.52	−0.38
	ERG11b	Putative cytochrome P-450 lanosterol 14-alpha-demethylase; target enzyme of azole antifungal drugs; increased protein abundance in azole-resistant strains	0.96	−0.65
	ERG24	Ortholog(s) has delta-14-sterol reductase activity and roles in cellular response to drugs, ergosterol biosynthetic processes, filamentous growth of a population of unicellular organisms in response to a biotic stimulus, and pathogenesis	0.53	−0.32
	ERG25	Ortholog(s) has C-4 methylsterol oxidase activity, role in ergosterol biosynthetic process, and endoplasmic reticulum membrane and plasma membrane localizations	1.02	−0.41
	ERG29	Ortholog(s) has roles in cellular iron ion homeostasis, ergosterol biosynthetic process, and mitochondrion organization and has endoplasmic reticulum and nuclear envelope localizations	0.84	−0.43
	HES1b	Ortholog(s) has oxysterol binding, sterol transporter activity, and roles in endocytosis, exocytosis, maintenance of cell polarity, piecemeal microautophagy of the nucleus, and sterol transport	1.48	−0.96
	CYB5	Ortholog(s) has electron carrier activity, role in ergosterol biosynthetic process, and endoplasmic reticulum membrane localization	0.73	−0.43
Lipid and fatty acid metabolism	CSR1b	Ortholog(s) has phosphatidylinositol transporter activity	0.59	−0.90
	HBN1	Ortholog(s) has oxidoreductase activity acting on NAD(P)H, nitrogenous group as acceptor activity, and roles in cellular response to oxidative stress and negative regulation of fatty acid metabolic process	−0.51	−0.10
	CAGL0A03740gb	Ortholog(s) has roles in fatty acid beta-oxidation and long-chain fatty acid catabolic processes and has peroxisome localization	−0.53	1.13
Stress response	RTA1b	Putative protein involved in 7-aminocholesterol resistance; gene is upregulated in azole-resistant strains	0.80	0.51
	RAD14b	Ortholog(s) has damaged DNA binding, zinc ion binding activity, and roles in UV damage excision repair, nucleotide excision repair involved in interstrand cross-link repair, nucleotide excision repair, and DNA damage recognition	0.52	−0.53
	SSA3	Heat shock protein of the HSP70 family	−0.55	0.06
Nitrogen metabolism	PUT1b	Ortholog(s) has proline dehydrogenase activity, role in the proline-catabolic process to glutamate, and mitochondrion localization	0.57	0.72
	MEP2	Ortholog(s) has high-affinity secondary active ammonium transmembrane transporter activity and methylammonium transmembrane transporter activity	−0.50	−0.04
Carbon metabolism	PBI1b	Has domain(s) with predicted alcohol O-acetyltransferase activity and role in alcohol metabolic process	2.11	−1.93
	ATF2	Putative alcohol acetyltransferase involved in steroid detoxification; gene is upregulated in azole-resistant strains	0.70	−0.09
	MLS1b	Ortholog(s) has malate synthase activity; roles in acetate catabolic process, carbon utilization, fatty acid catabolic process, and glyoxylate cycle; and cytosol, glyoxysome, and peroxisomal matrix localizations	−0.53	0.74
Heme biosynthesis	HEM13b	Putative coproporphyrinogen III oxidase; protein differentially expressed in azole-resistant strains	0.81	−0.67
	HEM14b	Ortholog(s) has oxygen-dependent protoporphyrinogen oxidase activity, role in heme biosynthetic process; and cytosol, mitochondrial inner membrane, and nucleus localizations	0.51	−0.70
	HMX1	Ortholog(s) has heme oxygenase (decyclizing) activity and roles in cellular iron ion homeostasis, heme catabolic process, response to carbon monoxide, and response to oxidative stress	−0.62	0.40
Cytoskeleton/cell cycle	MSC7b	Ortholog(s) has role in reciprocal meiotic recombination and cytosol, endoplasmic reticulum, and nucleus localizations	0.88	−0.56
	NCE102	Ortholog(s) has roles in actin cytoskeleton organization, eisosome assembly, establishment of protein localization to the plasma membrane, negative regulation of protein phosphorylation, and more	−0.55	0.43
	XBP1	Ortholog(s) has RNA polymerase II transcription factor activity, sequence-specific DNA binding, and sequence-specific DNA binding activity	−0.69	0.47
	FMP45	Ortholog(s) has roles in ascospore formation and cellular response to drugs and has fungal-type cell wall organization	−0.69	0.47
Mitochondrial function	COX26	Ortholog(s) has mitochondrial respiratory chain complex IV and mitochondrial respiratory chain supercomplex localization	−0.64	0.12
Intracellular traffic	SRO7	Ortholog(s) has Rab GTPase binding and SNARE binding activities and roles in Golgi-to-plasma membrane transport, establishment of cell polarity, exocytosis, and small GTPase-mediated signal transduction	0.51	−0.09
Unknown function	CAGL0M11660gb	Has domain(s) with predicted hydrolase activity	0.67	1.81
	CAGL0G05632gb	Ortholog(s) has cytoplasm localization	−0.52	1.32
	CAGL0K07337gb	Has domain(s) with predicted ion channel activity, role in ion transport, and membrane localization	−0.63	0.66
	CAGL0A02277g	Protein of unknown function	−0.72	−0.11
	PET10	Ortholog(s) has lipid particle localization	−0.51	0.45
	MUP1	Protein of unknown function	−0.78	0.47
	SET4	Ortholog of S. cerevisiae SET4 and S. cerevisiae S288C YJL105W	1.14	−0.30
	CAGL0L06776g	Has domain(s) with predicted sequence-specific DNA binding and transcription factor activities, zinc ion binding activity, and role in regulation of transcription, DNA templated	0.85	0.33
	CAGL0L08547g	Protein of unknown function	0.76	−0.05
	CAGL0J00297g	Ortholog(s) has endoplasmic reticulum localization	0.63	−0.41
	CAGL0G00594g	Ortholog(s) has Golgi apparatus and endoplasmic reticulum localization	0.61	−0.31

^aThe effect of the CgRpn4 deletion on the expression pattern is also shown. FLC, fluconazole; ABC, ATP-binding cassette.

^bGenes whose expression levels are significantly altered in the absence of CgRpn4.