Background: The overexpression of the efflux transporter genes is one of the important
mechanisms of resistance in fungal pathogens such as Candida and Aspergillus species.
Objective: Here, the expression alterations of drug efflux transporter genes were evaluated in non-
Cyp51A voriconazole-resistant Aspergillus fumigatus isolates.
Methods: Six A. fumigatus isolates including four voriconazole-resistant isolates with and without
azole-resistance-related mutations in addition to two susceptible A. fumigatus isolates were selected
from 300 previously characterized A. fumigatus clinical and environmental isolates, received
during 2013-2015. In order to extract RNA, the minimum inhibitory concentrations
(MICs) for the isolates were determined according to the broth microdilution protocol regarding
the Clinical and Laboratory Standards Institute document M38-A2 (CLSI, 2008). Alteration in the
expression of AfuMDR1, AfuMDR2, AfuMDR3, AfuMDR4, Cyp51A, and atrF was studied using
the real-time polymerase chain reaction assay.
Results: Based on REST® output, significant overexpression of atrF, AfuMDR1, AfuMDR3, and
AfuMDR4/Cyp51A, atrF, AfuMDR2, AfuMDR4 genes was observed in the isolates without azoleresistance-
related mutations, respectively. No significant overexpression was seen in the isolates
with T34/L98H except for the AfuMDR3 and AfuMDR4(P<0.05).
Conclusion: Our results support the hypothesis that efflux pump transporters can contribute to
voriconazole resistance in A. fumigatus.