Characterization of ABC-Efflux Pump AflMDR2 in Voriconazole Resistant Isolates of Aspergillus flavus
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Authors
Jost, Kristen E.
Issue Date
2010
Type
Thesis
Language
en_US
Keywords
Alternative Title
Abstract
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.
Description
Citation
Publisher
Kalamazoo College
License
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