GSE196409
Candida parapsilosis Mdr1B and Cdr1B are drivers of Mrr1-mediated clinical fluconazole resistance
Previous work has demonstrated that non-synonymous mutations in the gene encoding the putative transcription factor CpMrr1 can influence fluconazole susceptibility; however, the direct contribution of these mutations and how they influence fluconazole resistance in clinical isolates is poorly understood. We identified ten non-synonymous CpMRR1 mutations in a collection of 35 fluconazole resistant clinical isolates. The mutations leading to the A854V, R479K, and I283R substitutions were further examined and found to be activating mutations leading to increased fluconazole resistance. In addition to CpMDR1, we identified  another major facilitator superfamily (MFS) transporter gene (CpMDR1B, CPAR2_603010) and an ATP-binding Cassette (ABC) transporter gene (CpCDR1B, CPAR2_304370), as being up-regulated in isolates carrying CpMRR1 activating mutations. Overall design: Comparing the gene expression of Candida parapsilosis azole-susceptible and -resistant isolates to corresponding strains containing SNPs in MRR1 or MRR1 gene corrected to wild-type sequence