TABLE 2.
Genes with differential expression in clinical isolates containing CpMrr1 mutation compared to wild type
| C. parapsilosis genea | C. albicans homologb | Fold changec |
Descriptiond | ||
|---|---|---|---|---|---|
| A854V vs WT | R479K vs WT | I283R vs WT | |||
| CPAR2_100480 | GRP2 | 518.37 | 4,861.44 | 201.2 | Similar to S. cerevisiae Gre2p (methylglyoxal reductase); expression increased in fluconazole- and voriconazole-resistant strains |
| GRP2 | GRP2 | 136.77 | 756.03 | 47.92 | Similar to S. cerevisiae Gre2p (methylglyoxal reductase); expression increased in fluconazole- and voriconazole-resistant strains |
| CPAR2_105750 | 107.7 | 8.08 | 24.03 | Has domain(s) with predicted DNA binding activity | |
| CPAR2_103330 | orf19.2812 | 12.32 | 88.35 | 11.11 | Protein of unknown function; expression increased in fluconazole- and voriconazole-resistant strains |
| CPAR2_103600 | orf19.320 | 11.77 | 69.14 | 24.01 | Protein of unknown function; expression increased in fluconazole- and voriconazole-resistant strains |
| CPAR2_603010 | MDR1 | 10.51 | 218.69 | 7 | Protein of unknown function; expression increased in fluconazole- and voriconazole-resistant strains; ortholog(s) localize to the endoplasmic reticulum |
| MDR1 | MDR1 | 9.41 | 43.78 | 14.33 | Member of the MDR family of major facilitator transporter superfamily; putative drug transporter; expression increased in fluconazole- and voriconazole-resistant strains |
| CPAR2_206630 | orf19.3544 | 8.66 | 75.34 | 15.97 | Protein of unknown function; expression increased in fluconazole- and voriconazole-resistant strains |
| CPAR2_103320 | 7.81 | 8 | 7.09 | Uncharacterized | |
| CPAR2_601840 | orf19.5517 | 7.61 | 57.44 | 8.14 | Putative alcohol dehydrogenase; expression increased in fluconazole- and voriconazole-resistant strains |
| CPAR2_401490 | GST2 | 6.53 | 30.58 | 5.36 | GST2/URE2 family protein; expression increased in fluconazole- and voriconazole-resistant strains |
| CPAR2_404080 | orf19.5860 | 4.9 | 9.56 | 6.12 | Protein of unknown function; expression increased in fluconazole- and voriconazole-resistant strains |
| SADH | ADH5 | 4.83 | 10.44 | 3.35 | Butyraldehyde dehydrogenase, carbonyl reductase involved in amino acid degradation pathways |
| CPAR2_701130 | PLB3 | 4.81 | 6.13 | 5.73 | Has domain(s) with predicted phospholipase activity and role in metabolic process, phospholipid catabolic process |
| CPAR2_404090 | orf19.345 | 4.64 | 5.13 | 6.38 | Putative succinate-semialdehyde dehydrogenase [NAD(P)+]; expression increased in fluconazole- and voriconazole-resistant strains |
| CPAR2_703250 | 4.6 | 24.67 | 5.76 | Protein of unknown function; expression increased in fluconazole- and voriconazole-resistant strains | |
| LPG20 | LPG20 | 4.5 | 43.42 | 9.14 | Aldo-keto reductase family protein; expression increased in fluconazole- and voriconazole-resistant strains |
| CPAR2_805920 | orf19.1075.1 | 4.5 | 15.54 | 3.65 | Uncharacterized |
| CPAR2_304370 | CDR1 | 4.35 | 15.28 | 5.82 | Has domain(s) with predicted ATP binding, ATPase activity, ATPase-coupled transmembrane transporter activity, nucleoside-triphosphatase activity, nucleotide binding activity |
| OYE32 | OYE32 | 4.13 | 14.15 | 3.17 | Protein of unknown function; expression increased in fluconazole- and voriconazole-resistant strains; ortholog(s) have role in cell redox homeostasis |
| CPAR2_702640 | orf19.6586 | 4.08 | 15.93 | 11.22 | Protein of unknown function; expression increased in fluconazole- and voriconazole-resistant strains |
| CPAR2_701460 | orf19.7306 | 4 | 9.32 | 7.67 | Aldo-keto reductase family protein; expression increased in fluconazole- and voriconazole-resistant strains |
| CPAR2_300590 | FLU1 | 3.33 | 3.91 | 2.96 | Has domain(s) with predicted transmembrane transporter activity, role in transmembrane transport and integral component of membrane localization |
| CPAR2_503210 | orf19.6943 | 3.23 | 5.29 | 2.91 | Uncharacterized |
| CPAR2_402120 | orf19.1430 | 3.22 | 3.24 | 2.88 | Protein of unknown function; expression increased in fluconazole- and voriconazole-resistant strains |
| CPAR2_807720 | POX1-3 | 3.21 | 2.82 | 3.27 | Ortholog(s) have role in fatty acid beta-oxidation, long-chain fatty acid catabolic process and peroxisome localization |
| PDR16 | PDR16 | 3 | 3.61 | 2.82 | Phosphatidylinositol transfer protein; expression increased in fluconazole- and voriconazole-resistant strains |
| CPAR2_301750 | orf19.4779 | 2.9 | 3.23 | 2.03 | Has domain(s) with predicted transmembrane transporter activity, role in transmembrane transport and integral component of membrane localization |
| CPAR2_103670 | orf19.2446 | 2.88 | 8.42 | 5.36 | Protein of unknown function; expression increased in fluconazole- and voriconazole-resistant strains |
| CPAR2_109500 | orf19.6066 | 2.77 | 3.75 | 2.78 | Ortholog(s) have 4-hydroxybenzaldehyde dehydrogenase activity, carboxylate reductase activity |
| STP4 | STP4 | 2.72 | 2.91 | 2.8 | Putative transcription factor with zinc finger DNA-binding motif; expression increased in fluconazole- and voriconazole-resistant strains |
| CPAR2_200870 | orf19.6600 | 2.67 | 2.9 | 2.05 | Ortholog(s) have phosphatidic acid transfer activity and role in cardiolipin metabolic process, phospholipid translocation, phospholipid transport, positive regulation of phosphatidylcholine biosynthetic process |
| CPAR2_702300 | orf19.7166 | 2.65 | 5.79 | 2.86 | Protein of unknown function; expression increased in fluconazole- and voriconazole-resistant strains; ortholog(s) localize to the Golgi apparatus and endoplasmic reticulum |
| CPAR2_700540 | orf19.7235 | 2.57 | 3.36 | 3.72 | Protein of unknown function; expression increased in fluconazole- and voriconazole-resistant strains |
| MRR1 | MRR1 | 2.47 | 9.22 | 3.36 | Regulator of MDR1 transcription; expression increased in fluconazole- and voriconazole-resistant strains |
| CPAR2_400630 | orf19.4609 | 2.45 | 3.32 | 2.88 | Protein of unknown function; expression increased in fluconazole- and voriconazole-resistant strains |
| CPAR2_701900 | orf19.1985 | 2.27 | 3.61 | 2.83 | Has domain(s) with predicted protein serine/threonine kinase activity, transferase activity, transferring phosphorus-containing groups activity and role in protein phosphorylation |
| CPAR2_602390 | orf19.3442 | 2.25 | 2.68 | 2.63 | Putative oxidoreductase; expression increased in fluconazole- and voriconazole-resistant strains |
| CPAR2_211640 | orf19.5785 | 2.17 | 3.08 | 4.66 | Uncharacterized |
| CPAR2_201400 | orf19.6348 | 2.1 | 4.02 | 2.84 | Putative ubiquitin thiolesterase; predicted role in ubiquitin-dependent protein catabolism; expression increased in fluconazole- and voriconazole-resistant strains |
| LAP4 | LAP4 | 2.04 | 4.43 | 3.12 | Similar to aminopeptidase I; expression increased in fluconazole- and voriconazole-resistant strains |
| CPAR2_203940 | −2.02 | −2.92 | −4.19 | Uncharacterized | |
| CPAR2_800070 | PGA28 | −2.13 | −4.8 | −4.36 | Ortholog of C. albicans SC5314: C7_03110W_A/PGA28 |
| CPAR2_106690 | DIP5 | −2.13 | −4.9 | −2.23 | Ortholog(s) have l-aspartate transmembrane transporter activity, l-glutamate transmembrane transporter activity, dicarboxylic acid transmembrane transporter activity |
| CPAR2_500170 | ZRT1 | −2.2 | −2.34 | −2.81 | Has domain(s) with predicted metal ion transmembrane transporter activity, role in metal ion transport, transmembrane transport and membrane localization |
| CPAR2_407280 | orf19.1370 | −2.34 | −5.5 | −3.43 | Ortholog of C. albicans SC5314: C2_09800C_A |
| CPAR2_102140 | ADH4 | −2.47 | −4.56 | −3.33 | Has domain(s) with predicted oxidoreductase activity and role in metabolic process |
| CPAR2_702930 | orf19.6475 | −2.57 | −4.77 | −2.99 | Ortholog of Candida metapsilosis: CMET_1690 |
| CPAR2_403560 | orf19.1318 | −2.57 | −2.89 | −3.05 | Ortholog of C. albicans SC5314: C4_03580W_A |
| CPAR2_601420 | orf19.3475 | −2.59 | −3.21 | −3.51 | Ortholog of C. albicans SC5314: C6_02330W_A |
| CPAR2_106680 | PUT4 | −2.65 | −3.87 | −2.91 | Has domain(s) with predicted amino acid transmembrane transporter activity, role in amino acid transmembrane transport, transmembrane transport and membrane localization |
| CPAR2_701480 | orf19.7300 | −2.71 | −11.84 | −7.32 | Ortholog of C. albicans SC5314: CR_09040W_A |
| CPAR2_403880 | −2.74 | −3.95 | −3.7 | Uncharacterized | |
| CPAR2_502450 | MRV4 | −3.29 | −5.43 | −6.65 | Ortholog of C. albicans SC5314: C5_04210C_A/MRV4 |
| CPAR2_103080 | GLX3 | −4.2 | −5.87 | −5.28 | Ortholog(s) have glyoxalase III activity, protein folding chaperone activity |
| HGT10 | HGT10 | −4.99 | −9.23 | −4.09 | Ortholog(s) have solute/proton symporter activity, role in glycerol transport, transmembrane transport and plasma membrane localization |
| TNA1 | TNA1 | −5.8 | −3.37 | −2.99 | Ortholog(s) have carboxylic acid transmembrane transporter activity and role in carboxylic acid transport, quinolinic acid transmembrane transport |
| CPAR2_502460 | MRV2 | −6.41 | −49.42 | −19.66 | Ortholog of S. cerevisiae: YDL218W, C. albicans SC5314: C5_04190W_A/MRV2 |
| CPAR2_701510 | SLP3 | −6.68 | −9.98 | −11.84 | Has domain(s) with predicted membrane localization |
| NAG4 | NAG3 | −8.41 | −4.32 | −6.87 | Has domain(s) with predicted transmembrane transporter activity, role in transmembrane transport and integral component of membrane localization |
| CPAR2_802720 | orf19.3232 | −11.99 | −5.19 | −3.3 | Has domain(s) with predicted transmembrane transporter activity, role in transmembrane transport and integral component of membrane localization |
| CPAR2_108370 | HGT1 | −12.9 | −5.89 | −13.54 | Has domain(s) with predicted transmembrane transporter activity, role in transmembrane transport and integral component of membrane, membrane localization |
| CPAR2_102120 | orf19.2633.1 | −20.74 | −5.08 | −11.07 | Uncharacterized |
| CPAR2_108340 | HGT2 | −33.69 | −8.52 | −7.04 | Has domain(s) with predicted transmembrane transporter activity, role in transmembrane transport and integral component of membrane, membrane localization |
a
CPAR2 identifier from genome annotation of C. parapsilosis, CDC317, Candida Genome Database. Gene name provided where available.
b
Candida albicans homologs are identified where possible from Candida Genome Database. Gene names provided may be true orthologs and best hits.
c
Fold change (≥2 or ≤−2) for clinical isolates with CpMRR1 mutation versus each clinical isolate with CpMRR1 corrected to wild type. Performed in 3 biological replicates with FDR P values or ≤ 0.05.
d
Gene descriptions taken from Candida Genome Database.