Molecular Mechanisms Of Transcription Factor-Caplp In The Development Of Multi-drug Resistance In Candida Albicans

[Abstract] It has been designed in this study to clarify the function of Cap1p as atranscription factor regulating the expression of some genes related to multidrugresistance, such as CDR1 and MDR1, and those genes encoding the target proteins ofsome antifungal drugs in Candida albican. Having been incubated in the presence offluconzole, the mRNA level of CAP1 increased and the MIC80 of these strains tofluconzole increased accordingly, indicating the development of drug resistance. In theCAP1 deficient strains, the transcription of drug resistant gene CDR1 could be detected,although it decreased dramatically comparing wild-type strains with CAP, indicating thatCAP1 is not the unique transcription factor of CDR1. When wild-type and CAP1overexpressive strains had been incubated in the presence of fluconzole, the mRNA levelof MDR1 increased significantly, while in CAP1 deficient strains, the transcription ofMDR1 could never be detected. With the deficiency of CAP1, the transcription of ERG7,ERG9, ERG11 could not be detected, while after incubating in the presence of fluconzole,the transcription of these genes developed again, which also indicate that CAP1 is not theunique transcription factor of ERG7, ERG9 and ERG11. With the deficiency of CAP1,cells wrinkled and contracted, infection ability weakened and growth cycle prolonged.The techniques of gene microarray and proteomics had also been taken in this study,TOP2 and the gene encoding arsenite transporter were found related to CAP1. Thefunctions of these genes related to CAP1 and the regularity between them are further tobe determined. These results indicatied that Cap1p is an important transcription factor inthe development of drug resistance in C. albicans.