Isolation and identification of trans-regulatory factors of CDR1 in Candida albicans

• Main Authors: Chin-Sheng Chi, 紀錦昇
• Other Authors: Yun-Liang Yang
• Format: Others
• Language: en_US
• Published: 2004
• Online Access: http://ndltd.ncl.edu.tw/handle/47440450355243950914

碩士 === 國立交通大學 === 生物科技系所 === 92 === Candida albicans derive their importance not only from the severity of their infections but also for their ability to develop resistance against antifungals, such as azoles, in patients undergoing long-term or prophylactic treatment. Extensive biochemical studies have highlighted a significant diversity in the mechanisms conferring resistance to azoles. Up-regulation of drug extrusion pump-encoding genes belonging to the ABC (ATP binding cassette, e.g. CDR1 and CDR2) superfamily represents one of the most prevalent mechanisms of Candida drug resistance. In recent years, much effort has been devoted to understand the regulatory mechanisms of multi-drug transporter genes, such as CDR1, in C. albicans. Nonetheless, little is known about the trans-regulatory factors of CDR1. The study here focuses on isolation and identification of the trans-acting regulatory factors of CDR1. Using Ym00348 CDR1 promoter in-frame fusion with lacZ gene as the screening system, under the presence of drugs, four candidate open reading frames (ORFs) have been isolated. These four ORFs were named REP3, REP4, REP5, and REP6. Two (REP3 and REP6) of them have the C2H2 type zinc finger domain, which is one of the major nucleic acid-binding structures, indicating their potential roles as transcription regulators. According to the results of the Etest, rep3/rep3 homozygous mutant seems to be more susceptible to azoles. It shows that REP3 may have involved in the CDR1 expression and may also affect the drug susceptibility of C. albicans.