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Literature summary extracted from

  • Rybak, J.; Dickens, C.; Parker, J.; Caudle, K.; Manigaba, K.; Whaley, S.; Nishimoto, A.; Luna-Tapia, A.; Roy, S.; Zhang, Q.; Barker, K.; Palmer, G.; Sutter, T.; Homayouni, R.; Wiederhold, N.; Kelly, S.; Rogers, P.
    Loss of C-5 sterol desaturase activity results in increased resistance to azole and echinocandin antifungals in a clinical isolate of candida parapsilosis (2017), Antimicrob. Agents Chemother., 61, e00651-17 .
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

EC Number Cloned (Comment) Organism
1.14.19.20 gene ERG3, DNA and amino acid sequence determination and analysis Candida albicans
1.14.19.20 gene ERG3, DNA and amino acid sequence determination and analysis, transcriptome analysis Candida parapsilosis

Protein Variants

EC Number Protein Variants Comment Organism
1.14.19.20 G111R naturally occurring mutation, the mutant is obtained from a patient with prosthetic valve endocarditis, the mutant shows reduction in sterol desaturase activity and resistance to azole and echinocandin antifungals, replacement of both mutant alleles in the resistant isolate with the susceptible isolate's allele restores wild-type susceptibility to all azoles and echinocandins tested. Candida parapsilosis
1.14.19.20 additional information an ERG3 deletion construct for Candida albicans is generated by amplifying an ApaI-XhoI containing fragment consisting of flanking regions upstream from positions -350 to +39 relative to the start codon of Candida albicans ERG3 using primers CaERG3A-F and CaERG3B-R, as well as a NotI-SacIIcontaining fragment consisting of flanking regions from positions +997 to +1677 downstream of the start codon using primers CaERG3C-F and CaERG3D-R. These upstream and downstream fragments are cloned upstream and downstream, respectively, of the SAT1-flipper cassette in plasmid pSFS2, resulting in pCaERG3M1 Candida albicans
1.14.19.20 additional information an ERG3 deletion construct for Candida parapsilosis is generated by amplifying an ApaI-XhoI-containing fragment consisting of flanking regions upstream from positions -280 to +51 relative to the start codon of Candida parapsilosis ERG3 using primers ERG3-A and ERG3-B, as well as a NotI-SacII-containing fragment consisting of downstream flanking regions from positions +1047 to +1868 using primers ERG3-C and ERG3-D. These upstream and downstream fragments of ERG3 are cloned upstream and downstream, respectively, of the SAT1-flipper cassette in plasmid pSFS2 to result in plasmid p77ERG3 Candida parapsilosis

Inhibitors

EC Number Inhibitors Comment Organism Structure
1.14.19.20 posaconazole
-
 Candida albicans

Organism

EC Number Organism UniProt Comment Textmining
1.14.19.20 Candida albicans Q59VG6
-
-
1.14.19.20 Candida parapsilosis A0A1L2BH72
-
-
1.14.19.20 Candida parapsilosis CDC317 A0A1L2BH72
-
-

Synonyms

EC Number Synonyms Comment Organism
1.14.19.20 C-5 sterol desaturase
-
 Candida parapsilosis
1.14.19.20 C-5 sterol desaturase
-
 Candida albicans

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
1.14.19.20 35
-
 assay at Candida parapsilosis
1.14.19.20 35
-
 assay at Candida albicans

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
1.14.19.20 7
-
 assay at Candida parapsilosis
1.14.19.20 7
-
 assay at Candida albicans

General Information

EC Number General Information Comment Organism
1.14.19.20 malfunction a mechanism of antifungal resistance in this organism affecting susceptibility to azole and echinocandin antifungals is found in a clinical isolate obtained from a patient with prosthetic valve endocarditis. Transcriptome analysis indicates differential expression of several genes in the resistant isolate, including upregulation of ergosterol biosynthesis pathway genes ERG2, ERG5, ERG6, ERG11, ERG24, ERG25, and UPC2. Whole-genome sequencing reveals that the resistant isolate possesses an ERG3 mutation resulting in a G111R amino acid substitution. Sterol profiles indicate a reduction in sterol desaturase activity as a result of this mutation. Replacement of both mutant alleles in the resistant isolate with the susceptible isolate's allele restores wild-type susceptibility to all azoles and echinocandins tested Candida parapsilosis
1.14.19.20 additional information sterol composition of wild-type isolate and ERG3 mutants, overview Candida parapsilosis
1.14.19.20 additional information sterol composition of wild-type isolate and ERG3 mutants, overview Candida albicans