Multidrug resistance in Candida albicans: disruption of the BENr gene

Abstract

The BENr gene of Candida albicans, which confers resistance on susceptible strains of Saccharomyces cerevisiae to six structurally and functionally unrelated drugs, was described recently (R. Ben-Yaacov, S. Knoller, G. Caldwell, J. M. Becker, and Y. Koltin, Antimicrob. Agents Chemother. 38:648-652, 1994). This gene bears similarity to membrane proteins encoding antibiotic resistance in prokaryotes and eukaryotes. The effect of disruption of this gene on viability and drug susceptibility was determined. The results indicate that the gene is not essential but its inactivation leads to susceptibility to three of the four drugs tested. Inactivation of this gene did not increase the susceptibility of the mutant to benomyl, suggesting that C. albicans has other mechanisms of resistance, some of which may be additional efflux pumps that confer resistance to this tubulin-destabilizing agent.

Candida albicans strains heterozygous and homozygous for mutations in mitogen-activated protein kinase signaling components have defects in hyphal development

“…The lack of dominance of the wild-type allele to the null allele has also been reported for the Candida drug transporter CaMDR and the Candida MKC1 gene, a homolog of the Saccharomyces MAPK SLT2͞MPK1. The heterozygotes of null mutations of these genes are more sensitive to inhibitors than the wild type (23,24).…”

Transcriptional Regulation of MDR1 , Encoding a Drug Efflux Determinant, in Fluconazole-Resistant Candida albicans Strains through an Mcm1p Binding Site

“…C. albicans cells lacking the MDR1 gene are hypersensitive to most of the drugs listed above (20). In two FLC R clinical isolates, deletion of MDR1 abolished the drug resistance phenotype of these strains, demonstrating that in these strains, fluconazole resistance was dependent on the overexpression of MDR1 (55).…”

Identification of promoter elements responsible for the regulation of MDR1 from Candida albicans, a major facilitator transporter involved in azole resistance

“…Overexpression and gene inactivation studies have shown that MDR1 confers specific resistance to fluconazole, benomyl, cycloheximide, benzotriazole, methotrexate, 4-nitroquinoline-N-oxide (4-NQO) and sulfomethuron methyl (Ben-Yaacov et al, 1994;Fling et al, 1991;Goldway et al, 1995;Wirsching et al, 2000b). Disruption of MDR1 causes an increased susceptibility to methotrexate, cycloheximide and 4-NQO (Goldway et al, 1995;Sanglard et al, 1996).…”