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Overexpression of Efflux Pump Genes is an Alternative Mechanism in Voriconazole Resistant Aspergillus fumigatus isolates Without Relative Mutations in CYP5A

Author(s):

Maryam Moazeni*, Narges Aslani, Mojtaba Nabili and Hamid Badali   Pages 1 - 7 ( 7 )

Abstract:


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, a significant overexpression of atrF, AfuMDR1, AfuMDR3, and AfuMDR4/Cyp51A, atrF, AfuMDR2, AfuMDR4 genes were observed in the isolates without azole-resistance-related mutations, respectively. No significant over expression 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.

Keywords:

Aspergillus Fumigatus, Efflux Pumps, Voriconazole, Mechanism Of Resistant, Overexpression

Affiliation:

Invasive fungi research centre, Mazandaran university of medical sciences, Sari, Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Department of Medical Sciences, Sari Branch, Islamic Azad University, Sari, Invasive fungi research centre, Mazandaran university of medical sciences, Sari



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