ArticleAntimicrobial agents and chemotherapy2011
Differential requirement of the transcription factor Mcm1 for activation of the Candida albicans multidrug efflux pump MDR1 by its regulators Mrr1 and Cap1.
Article in Antimicrobial agents and chemotherapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 50 citations in OpenAlex.
- Recurrent mutations in the stress regulator Cap1 reveal a trade-off between azole resistance and oxidative stress response in Candida albicans.PLoS biology · 2026Article
- Transcription factor Hap2p regulates antioxidant stress responses to maintain miconazole resistance inMycology · 2025Article
- Mutations inJournal of fungi (Basel, Switzerland) · 2024Article
- Review
- Review
- Transcriptional Response of Candida auris to the Mrr1 Inducers Methylglyoxal and Benomyl.mSphere · 2022Article
- Oxidative stress response pathways in fungi.Cellular and molecular life sciences : CMLS · 2022Review
- The evaluation of the overexpression of the ERG-11, MDR-1, CDR-1, and CDR-2 genes in fluconazole-resistant Candida albicans isolated from Ahvazian cancer patients with oral candidiasis.Journal of clinical laboratory analysis · 2022Article
- Balancing Positive and Negative Selection:mBio · 2021Article
- Mrr1 regulation of methylglyoxal catabolism and methylglyoxal-induced fluconazole resistance in Candida lusitaniae.Molecular microbiology · 2021Article
- Review
- Contributions ofAntimicrobial agents and chemotherapy · 2018Article
- Host-Pathogen Interactions Mediated by MDR Transporters in Fungi: As Pleiotropic as it Gets!Genes · 2018Review
- Research of Mrr1, Cap1 and MDR1 inExperimental and therapeutic medicine · 2018Article
- Candida albicans Swi/Snf and Mediator Complexes Differentially Regulate Mrr1-InducedAntimicrobial agents and chemotherapy · 2017Article
- Article
- Quinone derivatives isolated from the endolichenic fungus Phialocephala fortinii are Mdr1 modulators that combat azole resistance in Candida albicans.Scientific reports · 2016Article
- Transcriptional Control of Drug Resistance, Virulence and Immune System Evasion in Pathogenic Fungi: A Cross-Species Comparison.Frontiers in cellular and infection microbiology · 2016Review
- Induction of Candida albicans drug resistance genes by hybrid zinc cluster transcription factors.Antimicrobial agents and chemotherapy · 2015Article
- Article
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Authors and funding
5 authors at 3 institutions in 3 countries.
Funding
Abstract
Overexpression of the multidrug efflux pump Mdr1 causes increased fluconazole resistance in the pathogenic yeast Candida albicans. The transcription factors Mrr1 and Cap1 mediate MDR1 upregulation in response to inducing stimuli, and gain-of-function mutations in Mrr1 or Cap1, which render the transcription factors hyperactive, result in constitutive MDR1 overexpression. The essential MADS box transcription factor Mcm1 also binds to the MDR1 promoter, but its role in inducible or constitutive MDR1 upregulation is unknown. Using a conditional mutant in which Mcm1 can be depleted from the cells, we investigated the importance of Mcm1 for MDR1 expression. We found that Mcm1 was dispensable for MDR1 upregulation by H2O2 but was required for full MDR1 induction by benomyl. A C-terminally truncated, hyperactive Cap1 could upregulate MDR1 expression both in the presence and in the absence of Mcm1. In contrast, a hyperactive Mrr1 containing a gain-of-function mutation depended on Mcm1 to cause MDR1 overexpression. These results demonstrate a differential requirement for the coregulator Mcm1 for Cap1- and Mrr1-mediated MDR1 upregulation. When activated by oxidative stress or a gain-of-function mutation, Cap1 can induce MDR1 expression independently of Mcm1, whereas Mrr1 requires either Mcm1 or an active Cap1 to cause overexpression of the MDR1 efflux pump. Our findings provide more detailed insight into the molecular mechanisms of drug resistance in this important human fungal pathogen.
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