Sterol uptake in Candida glabrata: Rescue of sterol auxotrophic strains
Abstract
Candida glabrata is emerging as a more common and important human pathogen. It is less susceptible to azole antifungals than Candida albicans, thus, posing some unique treatment challenges. Previously undetected C. glabrata isolates were identified from clinical specimens by adding bile to the growth medium. Cholesterol was found to be the responsible ingredient in bile. Six bile-dependent isolates were characterized and were found to exhibit wild-type equivalent growth when provided human or bovine serum or free cholesterol. Sterol profiles of the 6 isolates and a C. glabrata matching wild-type strain not requiring cholesterol indicated that 2 were defective in squalene epoxidase (encoded by the ERG1 gene) activity, 3 were defective in lanosterol synthase (encoded by the ERG7 gene) activity, and the sixth was defective in heme biosynthesis. All 7 isolates produced profiles that contained cholesterol transported from the media. Because Saccharomyces cerevisiae mutants unable to synthesize heme will take up exogenous sterol under aerobic conditions, hem1 nulls of C. glabrata and C. albicans were generated and tested for growth on ergosterol media. Only the C. glabrata hem1 was able to grow indicating significant differences in exogenous sterol uptake between the 2 organisms. The ability of C. glabrata to replace ergosterol with host sterol may be responsible for its elevated azole resistance.
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?
C. albicans takes up sterols only under aerobic conditions during the post-exponential growth phase, a process independent of UPC2.
“Zavrel et al. found that C. albicans takes up sterols only under aerobic conditions during the post-exponentialgrowth phase, a process independent of UPC2 .”
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 [20]
Cites
Transformation of yeast by lithium acetate/single-stranded carrier DNA/polyethylene glycol method
Gietz, R. D., & Woods, R. A. (2002) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(02)50957-5 · Cited by 2,890 · see citing works
Calderone, R. (2012) · ASM Press eBooks · Cited by 912 · 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
Brandt, M. E. (2002) · Emerging infectious diseases · doi:10.3201/eid0808.020059 · Cited by 646 · see citing works
Vermitsky, J.-P., & Edlind, T. D. (2004) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.48.10.3773-3781.2004 · Cited by 285 · see citing works
Pfaller, M. A., Messer, S. A., Hollis, R. J., Jones, R. N., & Diekema, D. J. (2002) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.46.6.1723-1727.2002 · Cited by 232 · see citing works
Anti-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
Dumitru, ., Hornby, J. M., & Nickerson, K. W. (2004) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.48.7.2350-2354.2004 · Cited by 143 · 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
Crowley, J. H., Leak, F. W., Shianna, K. V., Tove, S., & Parks, L. W. (1998) · Journal of Bacteriology · doi:10.1128/jb.180.16.4177-4183.1998 · Cited by 123 · see citing works
Lorenz, R. T., & Parks, L. W. (1990) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.34.9.1660 · Cited by 104 · see citing works
Hazen, K. C., Baron, E. J., Colombo, A. L., Girmenia, C., Sánchez-Sousa, A., del Palacio, A., de BEDOUT, C., & Gibbs, D. L. (2003) · Journal of Clinical Microbiology · doi:10.1128/jcm.41.12.5623-5632.2003 · Cited by 96 · see citing works
Self-citationYeast Oxidosqualene Cyclase (Erg7p) Is a Major Component of Lipid Particles
Milla, P., Athenstaedt, K., Viola, F., Oliaro‐Bosso, S., Kohlwein, S. D., Daum, G., & Balliano, G. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m104195200 · Cited by 88 · see citing works
Redding, S. W., Kirkpatrick, W. R., Saville, S., Coco, B. J., White, W., Fothergill, A., Rinaldi, M., Eng, T., Patterson, T. F., & Lopez-Ribot, J. (2003) · Journal of Clinical Microbiology · doi:10.1128/jcm.41.2.619-622.2003 · Cited by 85 · see citing works
Pleiotropic mutations in Saccharomyces cerevisiae affecting sterol uptake and metabolism
Lewis, T. L., Keesler, G. A., Fenner, G. P., & Parks, L. W. (1988) · Yeast · doi:10.1002/yea.320040203 · Cited by 80 · see citing works
Porphyrin mutants of : Correlated lesions in sterol and fatty acid biosynthesis
Bard, M., Woods, R. A., & Haslam, J. M. (1974) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(74)90845-6 · Cited by 73 · see citing works
Self-citationRelationships between Respiration and Susceptibility to Azole Antifungals in <i>Candida glabrata</i>
Brun, S., Aubry, C., Lima, O., Filmon, R., Bergès, T., Chabasse, D., & Bouchara, J.-P. (2003) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.47.3.847-853.2003 · Cited by 64 · 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-citationCandida glabrata erg1 Mutant with Increased Sensitivity to Azoles and to Low Oxygen Tension
Tsai, H., Bard, M., Izumikawa, K., Krol, A. A., Sturm, A. M., Culbertson, N. T., Pierson, C. A., & Bennett, J. E. (2004) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.48.7.2483-2489.2004 · Cited by 56 · see citing works
Self-citationDepletion of the Squalene Synthase ( ERG9 ) Gene Does Not Impair Growth of Candida glabrata in Mice
Nakayama, H., Izuta, M., Nakayama, N., Arisawa, M., & Aoki, Y. (2000) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.44.9.2411-2418.2000 · Cited by 53 · see citing works
Isolation 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
Landl, K., Klösch, B., & Turnowsky, F. (1996) · PubMed · doi:10.1002/(sici)1097-0061(199605)12:6%3c609::aid-yea949%3e3.0.co;2-b · Cited by 40 · see citing works
Isolation of cholesterol-dependent Candida glabrata from clinical specimens
Hazen, K. C., Stei, J., Darracott, C., Breathnach, A. S., May, J., & Howell, S. A. (2005) · Diagnostic Microbiology and Infectious Disease · doi:10.1016/j.diagmicrobio.2004.12.006 · Cited by 32 · 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-citationPierson, C. A., Jia, N., Mo, C., Lees, N. D., Sturm, A. M., Eckstein, J., Barbuch, R., & Bard, M. (2004) · Medical Mycology · doi:10.1080/1369378032000141471 · Cited by 19 · see citing works
Self-citationMarcireau, C., Joets, J., Pousset, D., Guilloton, M., & Karst, F. (1996) · Yeast · doi:10.1002/(sici)1097-0061(199605)12:6 · Cited by 13 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Azole Antifungal Resistance in Candida albicans and Emerging Non-albicans Candida Species
Whaley, S. G., Berkow, E. L., Rybak, J. M., Nishimoto, A. T., Barker, K. S., & Rogers, P. D. (2017) · Frontiers in Microbiology · doi:10.3389/fmicb.2016.02173 · Cited by 900 · see citing works
Structural mechanism of ergosterol regulation by fungal sterol transcription factor Upc2
Yang, H., Tong, J., Lee, C. W., Ha, S., Eom, S. H., & Im, Y. J. (2015) · Nature Communications · doi:10.1038/ncomms7129 · Cited by 223 · see citing works
Lv, Q.-Z., Yan, L., & Jiang, Y.-Y. (2016) · Virulence · doi:10.1080/21505594.2016.1188236 · Cited by 133 · see citing works
Hull, C. M., Parker, J. E., Bader, O., Weig, M., Gross, U., Warrilow, A. G. S., Kelly, D. E., & Kelly, S. L. (2012) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.06253-11 · Cited by 113 · see citing works
Azole Resistance in Candida glabrata
Whaley, S. G., & Rogers, P. D. (2016) · Current Infectious Disease Reports · doi:10.1007/s11908-016-0554-5 · Cited by 85 · see citing works
Zavrel, M., Hoot, S. J., & White, T. C. (2013) · Eukaryotic Cell · doi:10.1128/ec.00345-12 · Cited by 86 · see citing works
Tsai, H.-F., Sammons, L. R., Zhang, X., Suffis, S. D., Su, Q., Myers, T. G., Marr, K. A., & Bennett, J. E. (2010) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00535-10 · Cited by 80 · see citing works
Ergosterol 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
Joshua, I., & Höfken, T. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18040772 · Cited by 40 · see citing works
- Authors
- 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., & Hazen, K. C.
- Affiliations
- Indiana University – Purdue University Indianapolis (US)
- Eli Lilly (United States) (US)
- St Thomas' Hospital (GB)
- University of Virginia Health System (US)
- Corresponding author
- Bard, Martin
- Venue
- Diagnostic Microbiology and Infectious Disease
- Publisher
- Elsevier BV
- Published
- 2005-08
- Volume
- 52
- Issue
- 4
- Pages
- 285-293
- ISSN
- 0732-8893 (ISSN-L)
- OpenAlex
- W2095159049
- Cited by
- 58
- References
- 26
- Citations by year
- 2025: 1 · 2024: 4 · 2023: 2 · 2022: 4 · 2021: 4 · 2020: 1 · 2019: 3 · 2018: 2 · 2017: 3 · 2016: 2 · 2015: 6 · 2014: 4 · 2013: 3 · 2012: 3
- FWCI
- 1.28
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diagnostic Microbiology and Infectious Disease (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Burroughs Wellcome Fund
- National Institutes of Health
- National Institute of General Medical Sciences (R01GM062104, GM 62104)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
- Keywords
- Candida glabrata, sterol uptake, sterol auxotrophy, cholesterol, squalene epoxidase, ERG1, lanosterol synthase, heme biosynthesis, azole resistance, ergosterol, Candida albicans
- MeSH terms
- Animals, Azoles, Candida albicans, Cattle, Cholesterol, Culture Media, Ergosterol, Fungal Proteins, Heme, Humans, Mutation, Sterols, Candida glabrata, Serum
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
