Deletion of the Candida glabrata ERG3 and ERG11 genes: effect on cell viability, cell growth, sterol composition, and antifungal susceptibility

Geber, A; Hitchcock, C A; Swartz, J E; Pullen, F S; Marsden, K E; Kwon-Chung, K J; Bennett, J E

doi:10.1128/aac.39.12.2708

Cited by 203Antifungal resistance and susceptibilityFungal and yeast genetics researchFungal Plant Pathogen Control

Deletion of the Candida glabrata ERG3 and ERG11 genes: effect on cell viability, cell growth, sterol composition, and antifungal susceptibility

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Geber, A, Hitchcock, C A, Swartz, J E, Pullen, F S, Marsden, K E, Kwon-Chung, K J, Bennett, J E·1995·Antimicrobial Agents and Chemotherapy

DOI 10.1128/aac.39.12.2708PMC PMC163017

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Abstract

We have cloned and sequenced the structural genes encoding the delta 5,6 sterol desaturase (ERG3 gene) and the 14 alpha-methyl sterol demethylase (ERG11 gene) from Candida glabrata L5 (leu2). Single and double mutants of these genes were created by gene deletion. The phenotypes of these mutants, including sterol profiles, aerobic viabilities, antifungal susceptibilities, and generation times, were studied. Strain L5D (erg3 delta::LEU2) accumulated mainly ergosta-7,22-dien-3 beta-ol, was aerobically viable, and remained susceptible to antifungal agents but had a slower generation time than its parent strain. L5LUD (LEU2 erg11 delta::URA3) strains required medium supplemented with ergosterol and an anaerobic environment for growth. A spontaneous aerobically viable mutant, L5LUD40R (LEU erg11 delta::URA3), obtained from L5LUD (LEU2 erg11 delta::URA3), was found to accumulate lanosterol and obtusifoliol, was resistant to azole antifungal agents, demonstrated some increase in resistance to amphotericin B, and exhibited a 1.86-fold increase in generation time in comparison with L5 (leu2). The double-deletion mutant L5DUD61 (erg3 delta::LEU2 erg11 delta::URA3) was aerobically viable, produced mainly 14 alpha-methyl fecosterol, and had the same antifungal susceptibility pattern as L5LUD40R (LEU2 erg11 delta::URA3), and its generation time was threefold greater than that of L5 (leu2). Northern (RNA) analysis revealed that the single-deletion mutants had a marked increase in message for the undeleted ERG3 and ERG11 genes. These results indicate that differences in antifungal susceptibilities and the restoration of aerobic viability exist between the C. glabrata ergosterol mutants created in this study and those sterol mutants with similar genetic lesions previously reported for Saccharomyces cerevisiae.

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ERG3 deletion in C. glabrata does not affect fluconazole susceptibility.
“earlier work showing that ERG3 deletion in C. glabrata does not affect flz susceptibility.29”
From Narrow mutational signatures drive acquisition of multidrug resistance in the fungal pathogen Candida glabrata (2021) · cites this paper as [29]
CgCDR1, CgCDR2, CgSNQ2, CgPDR1 and CgERG11 code for plasma membrane ABC transporters, a zinc finger transcriptional regulator of pleiotropic drug resistance genes, and lanosterol 14-α-demethylase (target of fluconazole), respectively.
“These five genes, CgCDR1, CgCDR2, and CgSNQ2, CgPDR1 and CgERG11, code for plasma membrane ATP-binding cassette transporters, zinc finger transcriptional regulator of pleiotropic drug resistance genes, and lanosterol 14-␣-demethylase (target of fluconazole), respectively (7,9,11,12).”
From The Rho1 GTPase-activating protein CgBem2 is required for survival of azole stress in Candida glabrata (2011) · cites this paper as [7]

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Thompson, E., & Parks, L. W. (1974) · Journal of Bacteriology · doi:10.1128/jb.120.2.779-784.1974 · Cited by 43 · see citing works

Authors: Geber, A., Hitchcock, C. A., Swartz, J. E., Pullen, F. S., Marsden, K. E., Kwon-Chung, K. J., & Bennett, J. E.
Affiliations: George Washington University (US)
ORCID: Hitchcock, C A
Bennett, J E
Venue: Antimicrobial Agents and Chemotherapy
Publisher: American Society for Microbiology
Published: 1995-12
Volume: 39
Issue: 12
Pages: 2708-2717
ISSN: 0066-4804 (ISSN-L)
1098-6596
DOI: 10.1128/aac.39.12.2708
PMC: PMC163017
OpenAlex: W2121069993
Cited by: 203
References: 34
Citations by year: 2026: 5 · 2025: 8 · 2024: 9 · 2023: 14 · 2022: 10 · 2021: 11 · 2020: 4 · 2019: 4 · 2018: 5 · 2017: 8 · 2016: 2 · 2015: 4 · 2014: 11 · 2013: 6 · 2012: 8
FWCI: 5.30
Type: journal article
Language: en
Open access: green
europepmc.org
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
Locations: Antimicrobial Agents and Chemotherapy (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
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 › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Fungal Plant Pathogen Control
Keywords: Candida glabrata, ERG3, ERG11, deletion mutants, sterol composition, ergosterol, azole resistance, amphotericin B resistance, generation time, lanosterol, obtusifoliol
MeSH terms: Antifungal Agents, Base Sequence, Candida, Cloning, Molecular, Cytochrome P-450 Enzyme System, DNA, Fungal, Genes, Fungal, Leucine, Molecular Sequence Data, Nucleic Acid Hybridization, Oxidoreductases, Sterols, Transformation, Genetic, Blotting, Northern, Gene Deletion, Sterol 14-Demethylase

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Deletion of the Candida glabrata ERG3 and ERG11 genes: effect on cell viability, cell growth, sterol composition, and antifungal susceptibility

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