当前位置： SCI文献检索 > ANTIMICROBIAL AGENTS AND CHEMOTHERAPY期刊下所有文献 > Functional similarities and differences between Candida albicans Cdr1p and Cdr2p transporters.

Functional similarities and differences between Candida albicans Cdr1p and Cdr2p transporters.

Abstract：

:The Candida albicans CDR1 and CDR2 genes code for highly homologous ATP-binding cassette (ABC) transporters which are overexpressed in azole-resistant clinical isolates and which confer resistance to multiple drugs by actively transporting their substrates out of the cells. These transporters are formed by two homologous halves, each with an intracellular domain containing an ATP-binding site followed by a membrane-associated domain. We have expressed Cdr1p and Cdr2p in Saccharomyces cerevisiae to investigate their functions. The two proteins were properly expressed and functional, as determined by Western blotting, drug susceptibility assays, and rhodamine efflux. Using total membrane proteins from these transformants, we showed that Cdr1p and Cdr2p bind to the photoreactive analogue of rhodamine 123, [(125)I]iodoaryl azido-rhodamine 123 (IAARh123). IAARh123 photoaffinity labeling of membranes prepared from cells expressing either the N half or the C half of Cdr2p, or both, demonstrated that both halves contribute to rhodamine binding and can bind to rhodamine independently. Interestingly, Cdr1p was found to confer hypersusceptibility to FK520, an immunosuppressant and antifungal agent, whereas Cdr2p conferred resistance to this compound, uncovering a major functional difference between the two transporters. Furthermore, when administered in combination with azoles, FK520 sensitized cells expressing CDR1 but not those expressing CDR2. Finally, we showed that Cdr2p confers hypersusceptibility to hydrogen peroxide and resistance to diamide, while Cdr1p has no effect against these oxidative agents. Taken together, our results demonstrate that, despite a high level of structural conservation, Cdr1p and Cdr2p exhibit major functional differences, suggesting distinct biological functions.

journal_name

Antimicrob Agents Chemother

journal_title

Antimicrobial agents and chemotherapy

authors

Gauthier C,Weber S,Alarco AM,Alqawi O,Daoud R,Georges E,Raymond M

doi

10.1128/aac.47.5.1543-1554.2003

subject

Has Abstract

pub_date

2003-05-01 00:00:00

pages

1543-54

issue

eissn

0066-4804

issn

1098-6596

journal_volume

pub_type

杂志文章

在线工具

Functional similarities and differences between Candida albicans Cdr1p and Cdr2p transporters.