Keyword search (4,164 papers available)

"Cowen LE" Authored Publications:

Title Authors PubMed ID
1 The Canadian Fungal Research Network: current challenges and future opportunities. Horianopoulos LC, Gluck-Thaler E, Benoit Gelber I, Cowen LE, Geddes-McAlister J, Landry CR, Schwartz IS, Scott JA, Sellam A, Sheppard DC, Spribille T, Subramaniam R, Walker AK, Harris SD, Shapiro RS, Gerstein A 32717148
BIOLOGY
2 Tuning Hsf1 levels drives distinct fungal morphogenetic programs with depletion impairing Hsp90 function and overexpression expanding the target space. Veri AO, Miao Z, Shapiro RS, Tebbji F, O'Meara TR, Kim SH, Colazo J, Tan K, Vyas VK, Whiteway M, Robbins N, Wong KH, Cowen LE 29590106
BIOLOGY
3 Functional divergence of a global regulatory complex governing fungal filamentation. Polvi EJ, Veri AO, Liu Z, Hossain S, Hyde S, Kim SH, Tebbji F, Sellam A, Todd RT, Xie JL, Lin ZY, Wong CJ, Shapiro RS, Whiteway M, Robbins N, Gingras AC, Selmecki A, Cowen LE 30615616
BIOLOGY
4 Beauvericin Potentiates Azole Activity via Inhibition of Multidrug Efflux, Blocks Candida albicans Morphogenesis, and Is Effluxed via Yor1 and Circuitry Controlled by Zcf29. Shekhar-Guturja T, Tebung WA, Mount H, Liu N, Köhler JR, Whiteway M, Cowen LE 27736764
BIOLOGY

 

Title:Beauvericin Potentiates Azole Activity via Inhibition of Multidrug Efflux, Blocks Candida albicans Morphogenesis, and Is Effluxed via Yor1 and Circuitry Controlled by Zcf29.
Authors:Shekhar-Guturja T,  Tebung WA,  Mount H,  Liu N,  Köhler JR,  Whiteway M,  Cowen LE
Link:https://www.ncbi.nlm.nih.gov/pubmed/27736764?dopt=Abstract
Publication:
Keywords:
PMID:27736764 Category:Antimicrob Agents Chemother Date Added:2019-05-31
Dept Affiliation: BIOLOGY
1 Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
2 Department of Chemistry and Biochemistry, Concordia University, Montréal, Québec, Canada.
3 Division of Infectious Diseases, Boston Children's Hospital/Harvard Medical School, Boston, Massachusetts, USA.
4 Department of Biology, Concordia University, Montréal, Québec, Canada.
5 Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada leah.cowen@utoronto.ca.

Description:

Beauvericin Potentiates Azole Activity via Inhibition of Multidrug Efflux, Blocks Candida albicans Morphogenesis, and Is Effluxed via Yor1 and Circuitry Controlled by Zcf29.

Antimicrob Agents Chemother. 2016 12;60(12):7468-7480

Authors: Shekhar-Guturja T, Tebung WA, Mount H, Liu N, Köhler JR, Whiteway M, Cowen LE

Abstract

Invasive fungal infections are a leading cause of human mortality. Effective treatment is hindered by the rapid emergence of resistance to the limited number of antifungal drugs, demanding new strategies to treat life-threatening fungal infections. Here, we explore a powerful strategy to enhance antifungal efficacy against leading human fungal pathogens by using the natural product beauvericin. We found that beauvericin potentiates the activity of azole antifungals against azole-resistant Candida isolates via inhibition of multidrug efflux and that beauvericin itself is effluxed via Yor1. As observed in Saccharomyces cerevisiae, we determined that beauvericin inhibits TOR signaling in Candida albicans To further characterize beauvericin activity in C. albicans, we leveraged genome sequencing of beauvericin-resistant mutants. Resistance was conferred by mutations in transcription factor genes TAC1, a key regulator of multidrug efflux, and ZCF29, which was uncharacterized. Transcriptional profiling and chromatin immunoprecipitation coupled to microarray analyses revealed that Zcf29 binds to and regulates the expression of multidrug transporter genes. Beyond drug resistance, we also discovered that beauvericin blocks the C. albicans morphogenetic transition from yeast to filamentous growth in response to diverse cues. We found that beauvericin represses the expression of many filament-specific genes, including the transcription factor BRG1 Thus, we illuminate novel circuitry regulating multidrug efflux and establish that simultaneously targeting drug resistance and morphogenesis provides a promising strategy to combat life-threatening fungal infections.

PMID: 27736764 [PubMed - indexed for MEDLINE]




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