Voriconazole resistance in clinical and environmental isolates of Aspergillus flavus - frequency and investigation into the role of multidrug efflux pumps.

Voriconazole resistance in clinical and environmental isolates of Aspergillus flavus - frequency and investigation into the role of multidrug efflux pumps. Antimicrob Agents Chemother. 2018 Aug 20;: Authors: Paul RA, Rudramurthy SM, Dhaliwal M, Singh P, Ghosh AK, Kaur H, Varma S, Agarwal R, Chakrabarti A Abstract The magnitude of azole resistance in Aspergillus flavus and the underlying mechanism is obscure. We evaluated the frequency of azole resistance in a collection of clinical (n=121) and environmental isolates (n=68) of A. flavus by broth microdilution method. Six (5%) clinical isolates displayed voriconazole minimum inhibitory concentration (MIC) greater than the epidemiological cut-off value. Two of these isolates with non-wild-type MIC were isolated from same patient and were genetically distinct, which was confirmed by amplified length polymorphism. Mutations associated with azole resistance were not present in the lanosterol 14-α demethylase coding genes (cyp51A, cyp51B and cyp51C). Basal and voriconazole-induced expression of cyp51A homologs and various efflux pump genes was analyzed in three each of non-wild type and wild-type isolates. All the efflux pump genes screened showed low basal expression irrespective of the azole susceptibility of the isolate. However, the non-wild type isolates demonstrated heterogeneous overexpression of many efflux pumps and the target enzyme coding genes in response to induction with vori...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research