Objectives
<i>Candida glabrata</i> is one of the most common causes of <i>Candida</i> bloodstream infections worldwide. Some isolates of <i>C glabrata </i>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 <i>C glabrata </i>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 <i>C glabrata </i>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
Global prevalence and trends of fluconazole resistance in non-albicans Candida species: a systematic review and meta-analysis Xuehua Li, Mohammad Sholeh, Mahya Abedi Moghadam, Mahshid Ostadrahimi, Seyedeh Sedigheh Hosseini BMC Infectious Diseases.2026;[Epub] CrossRef
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Objectives
<i>Candida glabrata</i> has become one of the most common causes of <i>Candida</i> bloodstream infections worldwide. Some strains of <i>C. glabrata</i> 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 <i>C. glabrata</i> 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 <i>C. glabrata</i> strains were selected and used for further study. The expression of <i>CgCDR1</i> and <i>CgCDR2</i> genes was investigated by slot hybridization against fluconazole-susceptible, -resistant, and resistant-induced strains. In addition, <i>ERG3</i> and <i>ERG11</i> 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, <i>CgCDR1</i> gene was expressed more than <i>CgCDR2</i> gene in resistant strains. Though base substitution of <i>ERG11</i> and <i>ERG3</i> 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 <i>CgCDR1</i> gene was more closely related to fluconazole resistance of <i>C. glabrata</i> than <i>CgCDR2</i> gene. In addition, several other genes related with fluconazole resistance of <i>C. glabrata</i> were identified.
Citations
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Global prevalence and trends of fluconazole resistance in non-albicans Candida species: a systematic review and meta-analysis Xuehua Li, Mohammad Sholeh, Mahya Abedi Moghadam, Mahshid Ostadrahimi, Seyedeh Sedigheh Hosseini BMC Infectious Diseases.2026;[Epub] CrossRef
Whole genome sequencing analysis of Candida glabrata isolates collected from patients with selected drug-resistant candidiasis hospitalized in Eastern Poland Sebastian Kubica, Weronika Szulińska, Celina Kruszniewska-Rajs, Magdalena Kimsa-Dudek, Alina Olender, Agnieszka Bogut, Magdalena Szukała, Wojciech Dąbrowski, Daniel Pietrzak, Mariusz Gagoś, Joanna Magdalena Gola Folia Microbiologica.2025;[Epub] CrossRef
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