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Small-Scale Plasma Membrane Preparation for the Analysis of Candida albicans Cdr1-mGFPHis
Published on: June 13, 2021
R432 is a key residue for the multiple functions of Ndt80p in Candida albicans
Yun Liang Yang1, Chih Wei Wang, Shiang Ning Leaw
1Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan.
Abstract:
Ndt80p is an important transcription modulator to various stress-response genes in Candida albicans, the most common human fungal pathogen in systemic infections. We found that Ndt80p directly regulated its target genes, such as YHB1, via the mid-sporulation element (MSE). Furthermore, the ndt80(R432A) allele, with a reduced capability to bind MSE, failed to complement the defects caused by null mutations of NDT80. Thus, the R432 residue in the Ndt80p DNA-binding domain is involved in all tested functions, including cell separation, drug resistance, nitric oxide inactivation, germ tube formation, hyphal growth, and virulence. Hence, the importance of the R432 residue suggests a novel approach for designing new antifungal drugs by blocking the interaction between Ndt80p and its targets.
Insights
The transcription factor Ndt80p regulates stress genes in Candida albicans. A specific residue (R432) is crucial for its function, suggesting a new antifungal drug target.
Area of Science:
- Mycology
- Molecular Biology
- Pathogenesis
Background:
- Candida albicans is a major human fungal pathogen causing systemic infections.
- Ndt80p is a key transcription factor regulating stress-response genes in C. albicans.
Purpose of the Study:
- To investigate the role of Ndt80p in regulating target genes via the mid-sporulation element (MSE).
- To determine the significance of the R432 residue in Ndt80p's DNA-binding and functional activities.
Main Methods:
- Analysis of Ndt80p's direct regulation of target genes like YHB1 using MSE.
- Complementation studies using the ndt80(R432A) allele to assess the R432 residue's function.
Main Results:
- Ndt80p directly regulates genes including YHB1 through the MSE.
- The R432A mutation impaired Ndt80p's ability to bind MSE and complement null mutations.
- The R432 residue is essential for Ndt80p's roles in cell separation, drug resistance, nitric oxide inactivation, morphogenesis, and virulence.
Conclusions:
- The R432 residue in Ndt80p is critical for its DNA binding and diverse functions in Candida albicans.
- Targeting the Ndt80p-MSE interaction presents a potential strategy for developing novel antifungal therapies.
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