Functional genomics of bZIP transcriptional regulators in Candida albicans

Abstract

Candida albicans is an opportunistic fungal pathogen found in the normal newlinegastrointestinal flora of most healthy humans. However, in immuno-compromised newlinepatients, blood stream infections often cause death, despite the use of anti-fungal newlinetherapies. The growth and survival of all microbes is dependent upon their ability to newlinedetect and respond to envirolnnental changes. C. albicans virulence is a polygenic newlinetrait, one of which is its ability to undergo reversible morphological transitions newlinebetween yeast, pseudohyphal and hyphal growth forms. Numerous conditions newlinepromote yeast-hypha morphogenesis in vitro, including growth of C. albicans at newlinetemperatures gt35°C, serum, neutral pH and nutrient starvation. These presumably newlinereflect signals that control morphogenesis in vivo. Genetic analyses have revealed newlineother virulence factors including adhesion to host tissues, biofilm formation, and newlineability to use lipids as energy source via the glyoxylate pathway among others. A newlinegreat majority of transcriptional regulators functions by binding to promoter DNA and newlineup- or down-regulate transcription from target promoters. It has also been recognized newlinein studies from other systems that host-pathogen interaction causes genome-wide newlineexpression profile. Therefore it becomes important to identify and characterize the newlinefull complement of the transcriptional regulators that mediate these responses. newlineC. albicans genome size is -16 Mbp distributed in eight pairs of homologous newlinechromosomes which are numbered from 1 (largest) to 7 (smallest) and R (ribosomal newlineDNA). The assembly of complete C. albicans diploid genome sequence identified newline-14220 ORFs that are~ 100 amino acids and the full genome annotation has become newlinerecently available. Genome sequence analysis has uncovered many C. albicans ORFs newlinethat have similarity to S. cerevisiae and other fungi, but that are completely absent newlinefrom mammalian genomes. Theoretically, the products ofthese genes would! represent newlineattractive antifungal drug targets. Genome sequence analysis also revealed many newlineORFs that a