Journal article
Multidrug resistance in fungi: regulation of transporter-encoding gene expression
Frontiers in physiology, Vol.5, pp.143-143
2014
DOI: 10.3389/fphys.2014.00143
PMCID: PMC3997011
PMID: 24795641
Abstract
A critical risk to the continued success of antifungal chemotherapy is the acquisition of resistance; a risk exacerbated by the few classes of effective antifungal drugs. Predictably, as the use of these drugs increases in the clinic, more resistant organisms can be isolated from patients. A particularly problematic form of drug resistance that routinely emerges in the major fungal pathogens is known as multidrug resistance. Multidrug resistance refers to the simultaneous acquisition of tolerance to a range of drugs via a limited or even single genetic change. This review will focus on recent progress in understanding pathways of multidrug resistance in fungi including those of most medical relevance. Analyses of multidrug resistance in Saccharomyces cerevisiae have provided the most detailed outline of multidrug resistance in a eukaryotic microorganism. Multidrug resistant isolates of S. cerevisiae typically result from changes in the activity of a pair of related transcription factors that in turn elicit overproduction of several target genes. Chief among these is the ATP-binding cassette (ABC)-encoding gene PDR5. Interestingly, in the medically important Candida species, very similar pathways are involved in acquisition of multidrug resistance. In both C. albicans and C. glabrata, changes in the activity of transcriptional activator proteins elicits overproduction of a protein closely related to S. cerevisiae Pdr5 called Cdr1. The major filamentous fungal pathogen, Aspergillus fumigatus, was previously thought to acquire resistance to azole compounds (the principal antifungal drug class) via alterations in the azole drug target-encoding gene cyp51A. More recent data indicate that pathways in addition to changes in the cyp51A gene are important determinants in A. fumigatus azole resistance. We will discuss findings that suggest azole resistance in A. fumigatus and Candida species may share more mechanistic similarities than previously thought.
Details
- Title: Subtitle
- Multidrug resistance in fungi: regulation of transporter-encoding gene expression
- Creators
- Sanjoy Paul - Department of Molecular Physiology and Biophysics, Carver College of Medicine, University of Iowa Iowa City, IA, USAW Scott Moye-Rowley - Department of Molecular Physiology and Biophysics, Carver College of Medicine, University of Iowa Iowa City, IA, USA
- Resource Type
- Journal article
- Publication Details
- Frontiers in physiology, Vol.5, pp.143-143
- DOI
- 10.3389/fphys.2014.00143
- PMID
- 24795641
- PMCID
- PMC3997011
- NLM abbreviation
- Front Physiol
- ISSN
- 1664-042X
- eISSN
- 1664-042X
- Publisher
- Switzerland
- Grant note
- R01 GM049825 / NIGMS NIH HHS R21 AI092331 / NIAID NIH HHS
- Language
- English
- Date published
- 2014
- Academic Unit
- Molecular Physiology and Biophysics; Internal Medicine
- Record Identifier
- 9984025586402771
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