Overexpression of the
            <i>MDR1</i>
            Gene Is Sufficient To Confer Increased Resistance to Toxic Compounds in
            <i>Candida albicans</i>

Hiller, Davina; Sanglard, Dominique; Morschhäuser, Joachim

doi:10.1128/aac.00595-06

Cited by 25 publications

(33 citation statements)

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“…The ngs1D mutant was also slow to resume growth when the carbohydrate source was switched, and or when cells were switched from rich YPD medium to synthetic medium ( Figure 2 and Figures S1 and S2 in File S1). These results are consistent with reports that the Rep1 has other roles, including regulating the expression of the MDR1 drug efflux pump (Hiller et al 2006). Thus, Ngs1 does not specifically regulate the GlcNAc catabolic genes.…”

Section: Ngs1 Regulates Growth On Glcnac and Other Sugarssupporting

confidence: 92%

Regulation of Hyphal Growth and N-Acetylglucosamine Catabolism by Two Transcription Factors in Candida albicans

Naseem

Min

Spitzer³

et al. 2017

Genetics

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The amino sugar N-acetylglucosamine (GlcNAc) is increasingly recognized as an important signaling molecule in addition to its well-known structural roles at the cell surface. In the human fungal pathogen Candida albicans, GlcNAc stimulates several responses including the induction of the genes needed for its catabolism and a switch from budding to filamentous hyphal growth. We identified two genes needed for growth on GlcNAc (RON1 and NGS1) and found that mutants lacking these genes fail to induce the genes needed for GlcNAc catabolism. NGS1 was also important for growth on other sugars, such as maltose, but RON1 appeared to be specific for GlcNAc. Both mutants could grow on nonfermentable carbon sources indicating that they do not affect mitochondrial function, which we show is important for growth on GlcNAc but not for GlcNAc induction of hyphal morphogenesis. Interestingly, both the ron1D and ngs1D mutants were defective in forming hyphae in response to GlcNAc, even though GlcNAc catabolism is not required for induction of hyphal morphogenesis. The ron1D mutant showed a partial defect in forming hyphae, which was surprising since it displayed an elevated level of filamentous cells under noninducing conditions. The ron1D mutant also displayed an elevated basal level of expression of genes that are normally upregulated during hyphal growth. Consistent with this, Ron1 contains an Ndt80-like DNA-binding domain, indicating that it regulates gene expression. Thus, Ron1 is a key new component of the GlcNAc response pathway that acts as both an activator and a repressor of hyphal morphogenesis.

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Section: Ngs1 Regulates Growth On Glcnac and Other Sugarssupporting

confidence: 92%

Regulation of Hyphal Growth and N-Acetylglucosamine Catabolism by Two Transcription Factors in Candida albicans

Naseem

Min

Spitzer³

et al. 2017

Genetics

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“…In two FLC R clinical isolates, deletion of MDR1 abolished the drug resistance phenotype of these strains, demonstrating that in these strains, fluconazole resistance was dependent on the overexpression of MDR1 (55). Moreover, engineered overexpression of MDR1 confers increased resistance to some compounds (28).…”

mentioning

confidence: 95%

Transcriptional Regulation of MDR1 , Encoding a Drug Efflux Determinant, in Fluconazole-Resistant Candida albicans Strains through an Mcm1p Binding Site

Riggle

Kumamoto

2006

Eukaryot Cell

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“…Solubilized yeast proteins (10 ml) were separated by 10 % SDS-PAGE and transferred by Western blotting onto a nitrocellulose membrane. Immunodetection of Cdr1p, Cdr2p and Mdr1p was performed with polyclonal rabbit anti-Cdr1p, antiCdr2p and anti-Mdr1p antibodies as previously described (De Micheli et al, 2002;Hiller et al, 2006a) by chemoluminescence with an ECL kit according to the recommendations of the manufacturer (Amersham Biosciences).…”

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confidence: 99%

Divergent functions of three Candida albicans zinc-cluster transcription factors (CTA4, ASG1 and CTF1) complementing pleiotropic drug resistance in Saccharomyces cerevisiae

et al. 2008

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One of the mediators of pleiotropic drug resistance in Saccharomyces cerevisiae is the ABC-transporter gene PDR5. This gene is regulated by at least two transcription factors with Zn(2)-Cys(6) finger DNA-binding motifs, Pdr1p and Pdr3p. In this work, we searched for functional homologues of these transcription factors in Candida albicans. A C. albicans gene library was screened in a S. cerevisiae mutant lacking PDR1 and PDR3 and clones resistant to azole antifungals were isolated. From these clones, three genes responsible for azole resistance were identified. These genes (CTA4, ASG1 and CTF1) encode proteins with Zn(2)-Cys(6)-type zinc finger motifs in their N-terminal domains. The C. albicans genes expressed in S. cerevisiae could activate the transcription of a PDR5-lacZ reporter system and this reporter activity was PDRE-dependent. They could also confer resistance to azoles in a S. cerevisiae strain lacking PDR1, PDR3 and PDR5, suggesting that CTA4-, ASG1-and CTF1-dependent azole resistance can be caused by genes other than PDR5 in S. cerevisiae. Deletion of CTA4, ASG1 and CTF1 in C. albicans had no effect on fluconazole susceptibility and did not alter the expression of the ABC-transporter genes CDR1 and CDR2 or the major facilitator gene MDR1, which encode multidrug transporters known as mediators of azole resistance in C. albicans. However, additional phenotypic screening tests on the C. albicans mutants revealed that the presence of ASG1 was necessary to sustain growth on nonfermentative carbon sources (sodium acetate, acetic acid, ethanol). In conclusion, C. albicans possesses functional homologues of the S. cerevisiae Pdr1p and Pdr3p transcription factors; however, their properties in C. albicans have been rewired to other functions. INTRODUCTIONMultidrug transporters are widely distributed proteins in living organisms and are responsible for the transport of a large variety of compounds. Two types of transporters, the ATP-binding cassette (ABC) and the major facilitator superfamily (MFS) transporters have been described in lower eukaryotes such as Saccharomyces cerevisiae and have several functions, including phospholipid translocation in the plasma membrane, pheromone transport and the efflux of different classes of antifungal agents. Multidrug transporters are important for the human pathogen Candida albicans, as they have been found to be responsible for the development of resistance to azoles, which are important antifungal agents.In C. albicans, two ABC transporters, Cdr1p and Cdr2p (for Candida drug resistance) and one MFS transporter, Mdr1p (multidrug resistance) were shown to be upregulated in several azole-resistant isolates (Sanglard et al., 1995). Each of the genes encoding these proteins can be upregulated in distinct clinical azole-resistant strains. The transcription of the gene encoding Mdr1p, MDR1, is almost absent in azole-susceptible isolates, but is measurable in specific azole-resistant cells. The gene encoding Cdr1p, CDR1, shows basal transcriptional activity in azolesusceptible...

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Overexpression of the MDR1 Gene Is Sufficient To Confer Increased Resistance to Toxic Compounds in Candida albicans

Cited by 25 publications

References 0 publications

Regulation of Hyphal Growth and N-Acetylglucosamine Catabolism by Two Transcription Factors in Candida albicans

Regulation of Hyphal Growth and N-Acetylglucosamine Catabolism by Two Transcription Factors in Candida albicans

Transcriptional Regulation of MDR1 , Encoding a Drug Efflux Determinant, in Fluconazole-Resistant Candida albicans Strains through an Mcm1p Binding Site

Divergent functions of three Candida albicans zinc-cluster transcription factors (CTA4, ASG1 and CTF1) complementing pleiotropic drug resistance in Saccharomyces cerevisiae

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