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      https://www.ias.ac.in/article/fulltext/jbsc/026/03/0333-0339

    • Keywords

       

      CaMDR1 ; Candida albicans ; major facilitator; multidrug transporter

    • Abstract

       

      CaMDR1 encodes a major facilitator superfamily (MFS) protein inCandida albicans whose expression has been linked to azole resistance and which is frequently encountered in this human pathogenic yeast. In this report we have overexpressed CaMdr1p inSf9 insect cells and demonstrated for the first time that it can mediate methotrexate (MTX) and fluconazole (FLC) transport. MTX appeared to be a better substrate for CaMdr1p among these two tested drugs. Due to severe toxicity of these drugs to insect cells, further characterization of CaMdr1p as a drug transporter could not be done with this system. Therefore, as an alternative, CaMdr1p and Cdr1p, which is an ABC protein (ATP binding cassette) also involved in azole resistance inC. albicans, were independently expressed in a common hypersensitive host JG436 ofSaccharomyces cerevisiae. This allowed a better comparison between the functionality of the two export pumps. We observed that while both FLC and MTX are effluxed by CaMdr1p, MTX appeared to be a poor substrate for Cdr1p. JG436 cells expressing Cdr1p thus conferred resistance to other antifungal drugs but remained hypersensitive to MTX. Since MTX is preferentially transported by CaMdr1p, it can be used for studying the function of this MFS protein.

    • Author Affiliations

       

      Avmeet Kohli1 Vinita Gupta1 Shankarling Krishnamurthy1 2 Seyed E Hasnain1 3 Rajendra Prasad1

      1. Membrane Biology Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi - 110 067, India
      2. Heinrich-Heine-Universität, Institut für Mikrobiologie, Universitätsstr, 1/26.12, Düsseldorf - 40225, Germany
      3. Centre for DNA Fingerprinting and Diagnostics, ECIL Road, Nacharam, Hyderabad - 500 076, India
    • Dates

       
  • Journal of Biosciences | News

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