The RTA3 Gene, Encoding a Putative Lipid Translocase, Influences the Susceptibility of Candida albicans to Fluconazole
Open accessAbstract
The RTA3 gene, coding for a member of the Rta1p-like lipid-translocating exporter family, is coordinately upregulated with the ATP-binding cassette transporter genes CDR1 and CDR2 in azole-resistant clinical isolates of Candida albicans that carry activating mutations in the transcription factor Tac1p. We show here that deleting RTA3 in an azole-resistant clinical isolate carrying a Tac1p-activating mutation lowered fluconazole resistance by 2-fold, while overexpressing RTA3 in an azole-susceptible clinical isolate resulted in enhanced fluconazole tolerance associated with trailing growth in a liquid microtiter plate assay. We also demonstrate that an Rta3p-green fluorescent protein (GFP) fusion protein localizes predominantly to the plasma membrane, consistent with a putative function for Rta3p as a lipid translocase.
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RTA3 is associated with increased azole tolerance and trailing growth in C. albicans.
“RTA3, encoding a putative lipid translocase coordinately up-regulated with CDR1 in clinical isolates with Tac1 gain-of-function mutations, has been associated with increased azole tolerance and trailing growth in C. albicans.”
From Molecular and genetic basis of azole antifungal resistance in the opportunistic pathogenic fungus<i>Candida albicans</i> (2020) · cites this paper as [188]
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References 32 · Cited by 41
- Authors
- Whaley, S. G., Tsao, S., Weber, S., Zhang, Q., Barker, K. S., Raymond, M., & Rogers, P. D.
- Affiliations
- University of Tennessee Health Science Center (US)
- Institute for Research in Immunology and Cancer (CA)
- Venue
- Antimicrobial Agents and Chemotherapy
- Publisher
- American Society for Microbiology
- Published
- 2016-10
- Volume
- 60
- Issue
- 10
- Pages
- 6060-6066
- ISSN
- 0066-4804 (ISSN-L)
- 1098-6596
- PMC
- PMC5038240
- OpenAlex
- W2480735601
- Cited by
- 41
- References
- 32
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 4 · 2023: 4 · 2022: 3 · 2021: 11 · 2020: 3 · 2019: 6 · 2018: 3 · 2017: 3
- FWCI
- 3.69
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Antimicrobial Agents and Chemotherapy (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- HHS | NIH | National Institute of Allergy and Infectious Diseases (R01 AI058145)
- Canadian Institutes of Health Research (MOP 97734)
- 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 › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- Candida albicans, fluconazole resistance, azole resistance, CDR1, CDR2, ABC transporters, plasma membrane localization, antifungal susceptibility
- MeSH terms
- Antifungal Agents, Candida albicans, Fungal Proteins, Mutation, Recombinant Fusion Proteins, Transcription Factors, Transformation, Bacterial, Fluconazole, Gene Expression Regulation, Fungal, Protein Isoforms, Drug Resistance, Fungal, Membrane Transport Proteins, Phospholipid Transfer Proteins, Green Fluorescent Proteins
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