Molecular Biology and Genetics / Moleküler Biyoloji ve Genetik

Permanent URI for this collectionhttps://hdl.handle.net/11147/9

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Publisher: search.filters.publisher.American Society for Microbiology

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  • Article
    Citation - WoS: 7
    Citation - Scopus: 9
    Genomewide Elucidation of Drug Resistance Mechanisms for Systemically Used Antifungal Drugs Amphotericin B, Caspofungin, and Voriconazole in the Budding Yeast
    (American Society for Microbiology, 2019) Balkan, Çiğdem; Koç, Ahmet; Ercan, İlkcan; Akdeniz, Esra Şahin; Işık, Esin; Akdeniz, Esra Şahin; Balcıoğlu, Orhan; Kodedova, Marie; Koç, Ahmet; 04.03. Department of Molecular Biology and Genetics; 04. Faculty of Science; 01. Izmir Institute of Technology
    There are only a few antifungal drugs used systemically in treatment, and invasive fungal infections that are resistant to these drugs are an emerging problem in health care. In this study, we performed a high-copy-number genomic DNA (gDNA) library screening to find and characterize genes that reduce susceptibility to amphotericin B, caspofungin, and voriconazole in Saccharomyces cerevisiae. We identified the PDR16 and PMP3 genes for amphotericin B, the RMD9 and SWH1 genes for caspofungin, and the MRS3 and TRI1 genes for voriconazole. The deletion mutants for PDR16 and PMP3 were drug susceptible, but the other mutants had no apparent susceptibility. Quantitative-PCR analyses suggested that the corresponding drugs upregulated expression of the PDR16, PMP3, SWH1, and MRS3 genes. To further characterize these genes, we also profiled the global expression patterns of the cells after treatment with the antifungals and determined the genes and paths that were up-or downregulated. We also cloned Candida albicans homologs of the PDR16, PMP3, MRS3, and TRI1 genes and expressed them in S. cerevisiae. Heterologous expression of Candida homologs also provided reduced drug susceptibility to the budding yeast cells. Our analyses suggest the involvement of new genes in antifungal drug resistance.
  • Article
    Citation - WoS: 55
    Citation - Scopus: 64
    Identification of a Novel System for Boron Transport: Atr1 Is a Main Boron Exporter in Yeast
    (American Society for Microbiology, 2009) Kaya, Alaattin; Karakaya, Hüseyin Çağlar; Karakaya, Hüseyin Çağlar; Gladyshev, Vadim N.; Koç, Ahmet; 04.03. Department of Molecular Biology and Genetics; 04. Faculty of Science; 01. Izmir Institute of Technology
    Boron is a micronutrient in plants and animals, but its specific roles in cellular processes are not known. To understand boron transport and functions, we screened a yeast genomic DNA library for genes that confer resistance to the element in Saccharomyces cerevisiae. Thirty boron-resistant transformants were isolated, and they all contained the ATR1 (YML116w) gene. Atr1 is a multidrug resistance transport protein belonging to the major facilitator superfamily. C-terminal green fluorescent protein-tagged Atr1 localized to the cell membrane and vacuole, and ATR1 gene expression was upregulated by boron and several stress conditions. We found that atr1△ mutants were highly sensitive to boron treatment, whereas cells overexpressing ATR1 were boron resistant. In addition, atr1△ cells accumulated boron, whereas ATR1-overexpressing cells had low intracellular levels of the element. Furthermore, atr1△ cells showed stronger boron-dependent phenotypes than mutants deficient in genes previously reported to be implicated in boron metabolism. ATR1 is widely distributed in bacteria, archaea, and lower eukaryotes. Our data suggest that Atr1 functions as a boron efflux pump and is required for boron tolerance.