ArticleEukaryotic cell2012
A flucytosine-responsive Mbp1/Swi4-like protein, Mbs1, plays pleiotropic roles in antifungal drug resistance, stress response, and virulence of Cryptococcus neoformans.
Article in Eukaryotic cell, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 46 citations in OpenAlex.
- Genetic mutations in Cryptococcus neoformans pyrimidine salvage pathway enzymes contribute to reduced susceptibility against 5-fluorocytosine.npj antimicrobials and resistance · 2024Article
- BIOMOLECULAR ACTIVITY OF CRYPTOCOCCUS DURING CRYPTOCOCCOSIS: A REVIEW OF MOLECULAR INTERACTIONS OF CRYPTOCOCCUS WITH HUMAN IMMUNE SYSTEM AND BLOOD-BRAIN-BARRIER.African journal of infectious diseases · 2024Article
- Factors Influencing the Nitrogen-Source Dependent Flucytosine Resistance in Cryptococcus Species.mBio · 2023Article
- Combating increased antifungal drug resistance inActa biochimica et biophysica Sinica · 2023Review
- Essential Roles of Ribonucleotide Reductases under DNA Damage and Replication Stresses in Cryptococcus neoformans.Microbiology spectrum · 2022Article
- Uncontrolled transposition following RNAi loss causes hypermutation and antifungal drug resistance in clinical isolates of Cryptococcus neoformans.Nature microbiology · 2022Article
- Article
- Molecular Mechanisms of 5-Fluorocytosine Resistance in Yeasts and Filamentous Fungi.Journal of fungi (Basel, Switzerland) · 2021Review
- Cell Wall Integrity Pathway Involved in Morphogenesis, Virulence and Antifungal Susceptibility inJournal of fungi (Basel, Switzerland) · 2021Review
- Characterization of theInternational journal of molecular sciences · 2021Article
- Environmental Factors That Contribute to the Maintenance ofMicroorganisms · 2020Review
- Article
- Antiphagocytic protein 1 increases the susceptibility of Cryptococcus neoformans to amphotericin B and fluconazole.PloS one · 2019Article
- Nutrient and Stress Sensing in Pathogenic Yeasts.Frontiers in microbiology · 2019Review
- Characterization of the APSES-family transcriptional regulators of Histoplasma capsulatum.FEMS yeast research · 2018Article
- Flucytosine resistance in Cryptococcus gattii is indirectly mediated by the FCY2-FCY1-FUR1 pathway.Medical mycology · 2018Article
- The Cryptococcus neoformans Titan cell is an inducible and regulated morphotype underlying pathogenesis.PLoS pathogens · 2018Article
- The APSES transcription factor Vst1 is a key regulator of development in microsclerotium- and resting mycelium-producing Verticillium species.Molecular plant pathology · 2018Article
- Antifungal Therapy: New Advances in the Understanding and Treatment of Mycosis.Frontiers in microbiology · 2017Review
- Investigating Conservation of the Cell-Cycle-Regulated Transcriptional Program in the Fungal Pathogen, Cryptococcus neoformans.PLoS genetics · 2016Article
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Authors and funding
11 authors at 6 institutions in 2 countries.
Funding
Abstract
Cryptococcosis, caused by the basidiomycetous fungus Cryptococcus neoformans, is responsible for more than 600,000 deaths annually in AIDS patients. Flucytosine is one of the most commonly used antifungal drugs for its treatment, but its resistance and regulatory mechanisms have never been investigated at the genome scale in C. neoformans. In the present study, we performed comparative transcriptome analysis by employing two-component system mutants (tco1Δ and tco2Δ) exhibiting opposing flucytosine susceptibility. As a result, a total of 177 flucytosine-responsive genes were identified, and many of them were found to be regulated by Tco1 or Tco2. Among these, we discovered an APSES-like transcription factor, Mbs1 (Mbp1- and Swi4-like protein 1). Expression analysis revealed that MBS1 was regulated in response to flucytosine in a Tco2/Hog1-dependent manner. Supporting this, C. neoformans with the deletion of MBS1 exhibited increased susceptibility to flucytosine. Intriguingly, Mbs1 played pleiotropic roles in diverse cellular processes of C. neoformans. Mbs1 positively regulated ergosterol biosynthesis and thereby affected polyene and azole drug susceptibility. Mbs1 was also involved in genotoxic and oxidative stress responses. Furthermore, Mbs1 promoted production of melanin and capsule and thereby was required for full virulence of C. neoformans. In conclusion, Mbs1 is considered to be a novel antifungal therapeutic target for treatment of cryptococcosis.
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