Differential regulation of multidrug resistance gene(s) in the clinical isolates of pathogenic yeast Candida albicans

Abstract

Toxic compounds such as drugs are used to treat many diseases by killing the harmful target cells, which can be either foreign pathogenic organisms or the tumor cells of the patients. newlineHowever, both prokaryotic and eukaryotic cells can acquire the ability to become resistant to newlinetoxic compounds through the phenomenon of Multidrug (MDR) or Pleiotropic drug resistance newline(PDR). MDR is characterized by the cross-resistance of cells to a large number of structurally newlineand functionally unrelated cytotoxic compounds. The pathogenic yeast, Candida albicans can newlinealso acquire MDR, making it a valuable tool in the study of this phenomenon so that we may newlinegain insights into the mechanisms behind MDR in pathogenic fungi and in higher eukaryotes. newlineA common feature underlying acquisition of MDR in azole resistant clinical C. albicans newlineisolate is the over-expression of genes encoding plasma membrane A TP-binding cassette newline(ABC) drug efflux pump, CDR1 (Candida drug resistance 1) that causes :he expulsion of newlinedrugs from within the cell and, as a result, survival in the presence of these drugs. newlineResearch to overcome this problem in candidiasis chemotherapy has been focused mainly on newlinetwo areas: (1) development of Cdrl p modulators/inhibitors, (2) advanced and sensitive newlinedetection of CDR1 mRNA or Cdrlp and its expression regubtion. However, recent newlineunderstanding of the transcriptional regulation of efflux pump CDR 1 , provides new and newlineeffective avenues for the development of broad-spectrum fungicides in contrast to indirect newlineintervention via inhibition of the energy supply for drug efflux by modulators/inhibitors. newlineThe main focus of this study was, however, in processes different from the classical newlinetranscriptional control as majority of studies to date focus on the transcriptional regulation of CDR1 and relevance of the post-transcriptional events associated with it are poorly understood.