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KNQ1, a Kluyveromyces lactis gene encoding a drug efflux permease

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Abstract

Several transport systems play an important role in conferring multiple drug resistance, presumably due to their catalysis of the energy-dependent extrusion of a large number of structurally and functionally unrelated compounds out of the cells. In the present work, the gene named KNQ1 (encoding Kluyveromyces lactis membrane permease) was cloned by functional complementation of the cycloheximide-hypersensitivity phenotype of the Saccharomyces cerevisiae mutant strain lacking a functional PDR5 gene. The isolated gene exhibited 48.9% identity with the S. cerevisiae ATR1 gene conferring resistance to aminotriazole and 4-nitroquinoline-N-oxide and encoded a protein of 553 amino acids. When present in multicopy, it efficiently complemented the phenotype associated with the Δpdr5 or Δpdr1Δpdr3 mutations in S. cerevisiae. Overexpression of the KNQ1 gene in K. lactis wild-type strains led to resistance against several cytotoxic compounds, like 4-nitroquinoline-N-oxide, 3-aminotriazole, bifonazole and ketoconazole. The gene was assigned to K. lactis chromosome III and its expression was found to be responsive to oxidative stress induced by hydrogen peroxide. Based on the phenotype of homologous and heterologous transformants, we propose that the gene encodes a membrane-associated component of the machinery responsible for decreasing the concentration of several toxic compounds in the cytoplasm of yeast cells.

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Acknowledgements

Our thanks are due to R.A. Koistra and Y.H. Steensma for the generous gift of K. lactis chromosomal DNA blots and to Scott Moye-Rowley for the S. cerevisiae SCY2 strain. This work was supported by grants from the Slovak Grant Agency VEGA (1/0019/03), the Science and Technology Assistance Agency (APVT-51-000502), the European Community (QLK2-2001-002377), the Ministry of Education of the Slovak Republic and the Comenius University in Bratislava.

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  1. Faculty of Natural Sciences, Department of Microbiology and Virology, Comenius University in Bratislava, Mlynska dolina B-2, 842 15, Bratislava, Slovak Republic

    Maria Takacova, Denisa Imrichova, Jana Cernicka, Yvetta Gbelska & Julius Subik

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  1. Maria Takacova
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  2. Denisa Imrichova
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Correspondence to Julius Subik.

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Communicated by K. Breunig

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Takacova, M., Imrichova, D., Cernicka, J. et al. KNQ1, a Kluyveromyces lactis gene encoding a drug efflux permease. Curr Genet 45, 1–8 (2004). https://doi.org/10.1007/s00294-003-0449-5

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  • DOI: https://doi.org/10.1007/s00294-003-0449-5

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