1887

Abstract

The GenBank accession number for the sequence reported in this paper is AF188621.

Azole resistance in can be mediated by several resistance mechanisms. Among these, alterations of the azole target enzyme and the overexpression of multidrug efflux transporter genes are the most frequent. To identify additional putative azole resistance genes in , a genomic library from this organism was screened for complementation of fluconazole hypersusceptibility in YKKB-13 lacking the ABC (TP-inding assette) transporter gene . Among the genes obtained, a new gene was isolated and named (conazole resistance). The deduced amino acid sequence of showed similarity to (formerly ), a member of the major facilitator superfamily of multidrug efflux transporters. The expression of in YKKB-13 mediated not only resistance to fluconazole but also to cycloheximide among the different drugs tested. The disruption of in had only a slight effect on fluconazole susceptibility; however, it resulted in hypersusceptibility to mycophenolic acid, thus suggesting that this compound could be a substrate for the protein encoded by . Disruption of in a background of mutants with deletions in several multidrug efflux transporter genes, including , and , resulted in enhanced susceptibility to several azole derivatives. expression did not vary significantly between several pairs of azole-susceptible and azole-resistant clinical isolates. Therefore, seems not to be required for the development of azole resistance in clinical isolates.

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2000-11-01
2019-10-18
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