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- Proteomic Analysis of Cellular and Membrane Proteins in Fluconazole-Resistant
Candida glabrata - Jae Il Yoo, Chi Won Choi, Hwa Su Kim, Jung Sik Yoo, Young Hee Jeong, Yeong Seon Lee
- Osong Public Health Res Perspect. 2012;3(2):74-78. Published online June 30, 2012
- DOI: https://doi.org/10.1016/j.phrp.2012.04.001
- 3,161 View
- 18 Download
- 6 Crossref
-
Abstract
PDF - Objectives
Candida glabrata is one of the most common causes of Candida bloodstream infections worldwide. Some isolates of C glabrata may be intermediately resistant to azoles, with some strains developing resistance during therapy or prophylaxis with fluconazole. In this study, we used a proteomic approach to identify differentially expressed proteins between fluconazoleresistant and -susceptible strains.
Methods
Membrane and cellular proteins were extracted from fluconazolesusceptible and fluconazole-resistant C glabrata strains. Differentially expressed proteins were compared using two-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis. Proteins with >1.5-fold difference in expression were identified by liquid chromatography tandem mass spectrometry (LC-MS/MS).
Results
A total of 65 proteins were differentially expressed in the cellular and membrane fractions. Among the 39 cellular proteins, 11 were upregulated and 28 were downregulated in fluconazole-resistant strains in comparison with fluconazole-susceptible strains. In the membrane fraction, a total of 26 proteins were found, of which 19 were upregulated and seven were downregulated. A total of 31 proteins were identified by LC-MS/MS that are involved in glycolysis, carbohydrate transport, energy transfer, and other metabolic pathways. Heat shock proteins were identified in various spots.
Conclusion
Heat shock and stress response proteins were upregulated in the membrane fraction of the fluconazole-resistant C glabrata strain. Compared with susceptible strains, fluconazole-resistant strains showed increased expression of membrane proteins and decreased expression of cellular proteins. -
Citations
Citations to this article as recorded by
- What ‘Omics can tell us about antifungal adaptation
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FEMS Yeast Research.2022;[Epub] CrossRef - Effects of antifungal agents on the fungal proteome: informing on mechanisms of sensitivity and resistance
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Expert Review of Proteomics.2021; 18(3): 185. CrossRef - HPLC-MS identification and expression of Candida drug-resistance proteins from African HIV-infected patients
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AIMS Microbiology.2021; 7(3): 320. CrossRef - Transcriptional responses of Candida glabrata biofilm cells to fluconazole are modulated by the carbon source
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PROTEOMICS.2020;[Epub] CrossRef - Membrane Proteome-Wide Response to the Antifungal Drug Clotrimazole in Candida glabrata: Role of the Transcription Factor CgPdr1 and the Drug:H+ Antiporters CgTpo1_1 and CgTpo1_2
Pedro Pais, Catarina Costa, Carla Pires, Kiminori Shimizu, Hiroji Chibana, Miguel C. Teixeira
Molecular & Cellular Proteomics.2016; 15(1): 57. CrossRef
- What ‘Omics can tell us about antifungal adaptation
Original Article
- Gene Expression and Identification Related to Fluconazole Resistance of
Candida glabrata Strains - Jae Il Yoo, Chi Won Choi, Kyeong Min Lee, Yeong Seon Lee
- Osong Public Health Res Perspect. 2010;1(1):36-41. Published online December 31, 2010
- DOI: https://doi.org/10.1016/j.phrp.2010.12.009
- 3,267 View
- 19 Download
- 10 Crossref
-
Abstract
PDF
- Objectives
Candida glabrata has become one of the most common causes of Candida bloodstream infections worldwide. Some strains of C. glabrata may be intermediately resistant to all azoles. The several possible mechanisms of azole resistance have been reported previously, but the exact resistant mechanism is not clear. In this study, we identified differentially expressed genes (DEGs) of fluconazole-resistant C. glabrata and compared the gene expression of fluconazole-resistant strains with that of fluconazole-susceptible strains to identify gene corresponding to fluconazole resistance.
Methods
Using antifungal susceptibility test, several C. glabrata strains were selected and used for further study. The expression of CgCDR1 and CgCDR2 genes was investigated by slot hybridization against fluconazole-susceptible, -resistant, and resistant-induced strains. In addition, ERG3 and ERG11 genes were sequenced to analyze DNA base substitution. DEGs were identified by reverse transcription-polymerase chain reaction using DEG kit composed of 120 random primers.
Results
In slot hybridization, CgCDR1 gene was expressed more than CgCDR2 gene in resistant strains. Though base substitution of ERG11 and ERG3 genes was observed in several base sequences, just one amino acid change was identified in resistant strain. In the results of reverse transcription-polymerase chain reaction, 44 genes were upregulated and 34 genes were downregulated. Among them, adenosine triphosphate-binding cassette transporter-related genes, fatty acid desaturase, lyase, and hypothetical protein genes were upregulated and aldehyde dehydrogenase, oxidoreductase, and prohibitin-like protein genes were downregulated. Other DEGs were also identified.
Conclusion
This study showed that CgCDR1 gene was more closely related to fluconazole resistance of C. glabrata than CgCDR2 gene. In addition, several other genes related with fluconazole resistance of C. glabrata were identified. -
Citations
Citations to this article as recorded by- Two promising Bacillus-derived antifungal lipopeptide leads AF4 and AF5 and their combined effect with fluconazole on the in vitro Candida glabrata biofilms
Madduri Madhuri, Shivaprakash M. Rudramurthy, Utpal Roy
Frontiers in Pharmacology.2024;[Epub] CrossRef - Molecular Mechanisms Associated with Antifungal Resistance in Pathogenic Candida Species
Karolina M. Czajka, Krishnan Venkataraman, Danielle Brabant-Kirwan, Stacey A. Santi, Chris Verschoor, Vasu D. Appanna, Ravi Singh, Deborah P. Saunders, Sujeenthar Tharmalingam
Cells.2023; 12(22): 2655. CrossRef - Candida glabrata: Pathogenicity and Resistance Mechanisms for Adaptation and Survival
Yahaya Hassan, Shu Yih Chew, Leslie Thian Lung Than
Journal of Fungi.2021; 7(8): 667. CrossRef - Candidiasis and Mechanisms of Antifungal Resistance
Somanon Bhattacharya, Sutthichai Sae-Tia, Bettina C. Fries
Antibiotics.2020; 9(6): 312. CrossRef -
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