Relative Contribution of the ABC Transporters Cdr1, Pdh1, and Snq2 to Azole Resistance in Candida glabrata.

Relative Contribution of the ABC Transporters Cdr1, Pdh1, and Snq2 to Azole Resistance in Candida glabrata.
Antimicrob Agents Chemother. 2018 Jul 23;:
Authors: Whaley SG, Zhang Q, Caudle KE, Rogers PD
Abstract
The utility of the azole antifungals for the treatment of invasive candidiasis is severely hampered by azole resistance in Candida glabrata This resistance is mediated almost exclusively by activating mutations in the zinc cluster transcription factor Pdr1, which controls the genes encoding the multidrug resistance transporters Cdr1, Pdh1, and Snq2. However, the specific relative contribution of these transporters to resistance is not known. To address this question, the SAT1 flipper method was used to delete CDR1, PDH1, and SNQ2 in a strain of C. glabrata engineered to carry a clinically relevant activating mutation in PDR1. Susceptibility testing was performed according to the CLSI guidelines with minor modifications and confirmed with Etest strips. Of the single transporter deletion strains, only CDR1 deletion resulted in decreased azole MIC. Deletion of PDH1 in combination with CDR1 resulted in a moderate decrease in MIC from that observed with deletion of CDR1 alone. SNQ2 deletion only decreased the MIC in the triple deletion strain in the absence of both CDR1 and PDH1 Deletion of all three transporters in combination decreased the MIC to the level observed in the PDR1 deletion strains for some, but not all azoles tested, ...

Source: Antimicrobial Agents and Chemotherapy - July 23, 2018 Category: Microbiology Authors: Whaley SG, Zhang Q, Caudle KE, Rogers PD Tags: Antimicrob Agents Chemother Source Type: research