Characterization of ABC-Efflux Pump AflMDR2 in Voriconazole Resistant Isolates of Aspergillus flavus
Jost, Kristen E.
MetadataShow full item record
Aspergillus species are ubiquitous fungi that cause fatal respiratory tract infections in immunocompromised patients. Currently, the most commonly used drug to treat invasive aspergillosis infection is voriconazole (VCZ), but recent clinical studies have revealed multiple mechanisms of VCZ resistance in Aspergillus isolates. This study focuses on the upregulation of drug efflux pumps as a mode of resistance, specifically investigating the gene expression of an ATP-binding cassette transporter, AflMDR2, in VCZ resistant isolates of Aspergillus flavus. To obtain the levels of AflMDR2 expression, RNA was extracted from A. flavus isolates and quantified by quantitative reverse transcriptase-polymerase chain reaction techniques. All of the resistant isolates demonstrated AflMDR2 upregulation. When the isolates were treated with VCZ, AflMDR2 expression in the isolates both increased and decreased, indicating VCZ inhibition of AflMDR2 expression. These results also revealed a potential relationship between AflMDR2 upregulation and alternate mechanisms of resistance, suggesting that AflMDR2 upregulation plays a role in drug resistance only when coupled with other resistant mechanisms. Since very little has been published on Aspergillus flavus, further research is needed with respect to alternate mechanisms of resistance so that treatment can be improved to reduce the development of drug resistant Aspergillus strains.