Isolation, characterization, and regulation of the CandidaalbicansERG27 gene encoding the sterol 3-keto reductase
Abstract
The Candida albicans ERG27 gene which encodes the 3-keto reductase enzyme required for sterol C-4 demethylation was isolated and found to encode a 349 amino acid protein that is 60% identical at the amino acid level to the Saccharomyces cerevisiae Erg27p. A C. albicans erg27 null was created in a strain containing an integrated ERG27 rescue cassette under the control of the pMAL2 inducible promoter. The C. albicans erg27 strain was able to grow only in the presence of maltose indicating that the ERG27 gene is essential. The C. albicans erg27 null showed complete loss of both 3-keto reductase and oxidosqualene cyclase (Erg7p) activities compromising all sterol synthesis. These results suggest that Erg27p inhibitors might be effective antifungals. To explore ERG27 regulation, an erg11 null strain was generated. C. albicans erg6 and erg24 mutants were also employed along with the inhibitors, itraconazole and zaragozic acid A, to characterize ERG27 expression using Northern analysis. Expression was increased two- to fourfold in erg11, erg6 and erg24 backgrounds. However, itraconazole which targets Erg11p (lanosterol demethylase) increased ERG27 expression 10-fold and zaragozic acid A which targets the Erg9p (squalene synthase) increased ERG27 expression fivefold. The azole and erg11 results support other observations that azoles may affect non-sterol targets.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
ERG1, ERG7, ERG9, ERG25, ERG26, and ERG27 are essential, while ERG2, ERG3, ERG5, ERG6, and ERG24 are considered non-essential in ergosterol biosynthesis.
“By using the technology of gene disruption and controlled gene expression, ERG1 , ERG7 , ERG9 , ERG25 , ERG26 , and ERG27 have been proved to be essential, while ERG2 , ERG3 , ERG5 , ERG6 , and ERG24 are considered to be non-essential in ergosterol biosynthesis.”
From The synthesis, regulation, and functions of sterols in<i>Candida albicans</i>: Well-known but still lots to learn (2016) · cites this paper as [27]
Cites
Studies on the transformation of intact yeast cells by the LiAc/SS‐DNA/PEG procedure
Gietz, R. D., Schiestl, R. H., Willems, A. R., & Woods, R. A. (1995) · Yeast · doi:10.1002/yea.320110408 · Cited by 2,030 · see citing works
Isogenic strain construction and gene mapping in Candida albicans.
Fonzi, W. A., & Irwin, M. Y. (1993) · Genetics · doi:10.1093/genetics/134.3.717 · Cited by 1,695 · see citing works
Clinical, Cellular, and Molecular Factors That Contribute to Antifungal Drug Resistance
White, T. C., Marr, K. A., & Bowden, R. A. (1998) · Clinical Microbiology Reviews · doi:10.1128/cmr.11.2.382 · Cited by 1,353 · see citing works
Rapid Hypothesis Testing with Candida albicans through Gene Disruption with Short Homology Regions
Wilson, R. B., Davis, D. A., & Mitchell, A. P. (1999) · Journal of Bacteriology · doi:10.1128/jb.181.6.1868-1874.1999 · Cited by 763 · see citing works
White, T. C. (1997) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.41.7.1482 · Cited by 612 · see citing works
Sanglard, D., Ischer, F., Monod, M., & Bille, J. (1997) · Microbiology · doi:10.1099/00221287-143-2-405 · Cited by 587 · see citing works
White, T. C. (1997) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.41.7.1488 · Cited by 292 · see citing works
Gaber, R. F., Copple, D. M., Kennedy, B. K., Vidal, M., & Bard, M. (1989) · Molecular and Cellular Biology · doi:10.1128/mcb.9.8.3447 · Cited by 257 · see citing works
Self-citationHuman Mycoses: Drugs and Targets for Emerging Pathogens
Georgopapadakou, N. H., & Walsh, T. J. (1994) · Science · doi:10.1126/science.8153622 · Cited by 234 · see citing works
Henry, K. W., Nickels, J. T., & Edlind, T. D. (2000) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.44.10.2693-2700.2000 · Cited by 216 · see citing works
De Backer, M. D., Ilyina, T., Ma, X.-J., Vandoninck, S., Luyten, W. H. M. L., & Vanden Bossche, H. (2001) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.45.6.1660-1670.2001 · Cited by 211 · see citing works
Calabrese, D. R., Billé, J., & Sanglard, D. (2000) · Microbiology · doi:10.1099/00221287-146-11-2743 · Cited by 210 · see citing works
Watson, P. F., Rose, M. E., Ellis, S. W., England, H., & Kelly, S. L. (1989) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(89)91792-0 · Cited by 197 · see citing works
Primary Structure of the P450 Lanosterol Demethylase Gene from Saccharomyces cerevisiae
Kalb, V. F., Woods, C. W., Turi, T. G., Dey, C. R., Sutter, T. R., & LOPER, J. C. (1987) · DNA · doi:10.1089/dna.1987.6.529 · Cited by 176 · see citing works
Bard, M., Bruner, D. A., Pierson, C. A., Lees, N. D., Biermann, B. J., Frye, L. L., Koegel, C., & Barbuch, R. J. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.1.186 · Cited by 166 · see citing works
Self-citationAnti-CandidaDrugs — The Biochemical Basis for Their Activity
BOSSCHE, H. V., Willemsens, G., & Marichal, P. (1987) · CRC Critical Reviews in Microbiology · doi:10.3109/10408418709104448 · Cited by 145 · see citing works
Polyene Resistance and the Isolation of Sterol Mutants in Saccharomyces cerevisiae
Molzahn, S. W., & Woods, R. A. (1972) · Journal of General Microbiology · doi:10.1099/00221287-72-2-339 · Cited by 132 · see citing works
Bard, M., Lees, N. D., Turi, T. G., Craft, D., Cofrin, L., Barbuch, R. J., Koegel, C., & Loper, J. C. (1993) · Lipids · doi:10.1007/bf02537115 · Cited by 121 · see citing works
Self-citationJensen-Pergakes, K. L., Kennedy, M. A., Lees, N. D., Barbuch, R., Koegel, C., & Bard, M. (1998) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.42.5.1160 · Cited by 121 · see citing works
Self-citationRecent Developments in Molecular Genetics of Candida Albicans
Backer, M. D. D., Magee, P. T., & Plá, J. (2000) · Annual Review of Microbiology · doi:10.1146/annurev.micro.54.1.463 · Cited by 109 · see citing works
Gachotte, D. J., Barbuch, R. J., Gaylor, J. L., Nickel, E., & Bard, M. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.23.13794 · Cited by 100 · see citing works
Self-citationGachotte, D. J., Sen, S. E., Eckstein, J. A., Barbuch, R. J., Krieger, M., Ray, B. D., & Bard, M. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.22.12655 · Cited by 99 · see citing works
Self-citationA novel gene conserved from yeast to humans is involved in sterol biosynthesis
Gachotte, D. J., Eckstein, J. A., Barbuch, R. J., Hughes, T. R., Roberts, C., & Bard, M. (2001) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)32347-6 · Cited by 84 · see citing works
Self-citationSantos, M. A. S., Perreau, V. M., & Tuite, M. F. (1996) · The EMBO Journal · doi:10.1002/j.1460-2075.1996.tb00886.x · Cited by 83 · see citing works
Protein–protein interactions among C-4 demethylation enzymes involved in yeast sterol biosynthesis
Mo, C., Valachovič, M., Randall, S. K., Nickels, J. T., & Bard, M. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.112202799 · Cited by 81 · see citing works
Self-citationThe identification of a gene family in the Saccharomyces cerevisiae ergosterol biosynthesis pathway
LAI, M. H., Bard, M., Pierson, C. A., F.Alexander, J., Goebl, M. G., Carter, G. T., & Kirsch, D. R. (1994) · Gene · doi:10.1016/0378-1119(94)90728-5 · Cited by 69 · see citing works
Self-citationLorenz, R. T., & Parks, L. W. (1992) · DNA and Cell Biology · doi:10.1089/dna.1992.11.685 · Cited by 67 · see citing works
Brown, D. H., Slobodkin, I. V., & Kumamoto, C. A. (1996) · Molecular and General Genetics MGG · doi:10.1007/bf02174347 · Cited by 64 · see citing works
Evaluation of the CaMAL2 promoter for regulated expression of genes in Candida albicans
Backen, A. C., Broadbent, I. D., Fetherston, R., Rosamond, J., Schnell, N. F., & Stark, M. J. R. (2000) · Yeast · doi:10.1002/1097-0061(20000915)16:12 · Cited by 63 · see citing works
Construction and growth properties of a yeast strain defective in sterol 14-reductase
Marcireau, C., Guyonnet, D., & Karst, F. (1992) · Current Genetics · doi:10.1007/bf00317919 · Cited by 62 · see citing works
Jia, N., Arthington-Skaggs, B., Lee, W., Pierson, C. A., Lees, N. D., Eckstein, J., Barbuch, R., & Bard, M. (2002) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.46.4.947-957.2002 · Cited by 61 · see citing works
Self-citationGoshorn, A. K., Grindle, S. M., & Scherer, S. W. (1992) · Infection and Immunity · doi:10.1128/iai.60.3.876-884.1992 · Cited by 60 · see citing works
Gachotte, D. J., Pierson, C. A., Lees, N. D., Barbuch, R. J., Koegel, C., & Bard, M. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.21.11173 · Cited by 58 · see citing works
Self-citationMo, C., Milla, P., Athenstaedt, K., Ott, R. G., Balliano, G., Daum, G., & Bard, M. (2003) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/s1388-1981(03)00088-x · Cited by 47 · see citing works
Self-citationIsolation of Hem3 mutants from Candida albicans by sequential gene disruption
Kurtz, M. B., & Marrinan, J. A. (1989) · Molecular and General Genetics MGG · doi:10.1007/bf00330941 · Cited by 42 · see citing works
Characterization of a cytochrome P450 deficient mutant of Candidaalbicans
Bard, M., Lees, N. D., Barbuch, R. J., & Sanglard, D. (1987) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(87)91000-x · Cited by 34 · see citing works
Self-citationKennedy, M. A., Johnson, T. A., Lees, N. D., Barbuch, R., Eckstein, J. A., & Bard, M. (2000) · Lipids · doi:10.1007/s11745-000-0521-2 · Cited by 29 · see citing works
Self-citationAaron, K. E., Pierson, C. A., Lees, N. D., & Bard, M. (2001) · FEMS Yeast Research · doi:10.1111/j.1567-1364.2001.tb00020.x · Cited by 22 · see citing works
Self-citationPF1163A, a Novel Antifungal Agent, Inhibit Ergosterol Biosynthesis at C-4 Sterol Methyl Oxidase.
NOSE, H., Fushimi, H., Seki, A., Sasaki, T., Watabe, H., & Hoshiko, S. (2002) · The Journal of Antibiotics · doi:10.7164/antibiotics.55.969 · Cited by 21 · see citing works
Pirog, T., Kovalenko, M. A., & Kuz'minskaya, Y. V. (2003) · Microbiology · doi:10.1023/a:1024247915758 · Cited by 11 · see citing works
Phenotypes ofCandida albicanssterol mutants deficient in Δ8,7-isomerization or 5-desaturation
Shimokawa, O., & Nakyama, H. (1991) · Medical Mycology · doi:10.1080/02681219180000091 · Cited by 6 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Lv, Q.-Z., Yan, L., & Jiang, Y.-Y. (2016) · Virulence · doi:10.1080/21505594.2016.1188236 · Cited by 133 · see citing works
Sterol uptake in Candida glabrata: Rescue of sterol auxotrophic strains
Bard, M., Sturm, A. M., Pierson, C. A., Brown, S., Rogers, K. M., Nabinger, S., Eckstein, J., Barbuch, R., Lees, N. D., Howell, S. A., et al. (2005) · Diagnostic Microbiology and Infectious Disease · doi:10.1016/j.diagmicrobio.2005.03.001 · Cited by 58 · see citing works
Self-citationErgosterol Biosynthesis and Regulation Impact the Antifungal Resistance and Virulence of Candida spp
Eliaš, D., Tóth Hervay, N., & Gbelská, Y. (2024) · Stresses · doi:10.3390/stresses4040041 · Cited by 63 · see citing works
Feng, Y., Lu, H., Whiteway, M., & Jiang, Y. (2023) · Journal of Global Antimicrobial Resistance · doi:10.1016/j.jgar.2023.10.019 · Cited by 40 · see citing works
- Authors
- Pierson, C. A., Jia, N., Mo, C., Lees, N. D., Sturm, A. M., Eckstein, J., Barbuch, R., & Bard, M.
- Affiliations
- Indiana University – Purdue University Indianapolis (US)
- Eli Lilly (United States) (US)
- Corresponding author
- Pierson, C. A.
- Venue
- Medical Mycology
- Publisher
- Oxford University Press (OUP)
- Published
- 2004-01
- Volume
- 42
- Issue
- 5
- Pages
- 461-473
- ISSN
- 0268-1218 (ISSN-L)
- 1369-3786
- 1460-2709
- OpenAlex
- W2027579286
- Cited by
- 19
- References
- 41
- Citations by year
- 2024: 1 · 2023: 2 · 2020: 1 · 2019: 1 · 2016: 1 · 2012: 2
- FWCI
- 0.64
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Medical Mycology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Burroughs Wellcome Fund
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Plant biochemistry and biosynthesis
- Keywords
- Candida albicans, ergosterol biosynthesis, ERG6, gene expression regulation, itraconazole, zaragozic acid A, antifungal drug targets, oxidosqualene cyclase
- MeSH terms
- Amino Acid Sequence, Base Sequence, Candida albicans, Ergosterol, Genes, Fungal, Molecular Sequence Data, Oxidoreductases, Saccharomyces cerevisiae, Gene Expression Regulation, Fungal, Gene Deletion, Sequence Analysis, DNA, Genes, Essential, Saccharomyces cerevisiae Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review