Translation Inhibition by Rocaglates Activates a Species-Specific Cell Death Program in the Emerging Fungal Pathogen Candida auris.

MBio
Kali R IyerLeah E Cowen

Abstract

Fungal infections are a major contributor to infectious disease-related deaths worldwide. Recently, global emergence of the fungal pathogen Candida auris has caused considerable concern because most C. auris isolates are resistant to fluconazole, the most commonly administered antifungal, and some isolates are resistant to drugs from all three major antifungal classes. To identify novel agents with bioactivity against C. auris, we screened 2,454 compounds from a diversity-oriented synthesis collection. Of the five hits identified, most shared a common rocaglate core structure and displayed fungicidal activity against C. auris These rocaglate hits inhibited translation in C. auris but not in its pathogenic relative Candida albicans Species specificity was contingent on variation at a single amino acid residue in Tif1, a fungal member of the eukaryotic initiation factor 4A (eIF4A) family of translation initiation factors known to be targeted by rocaglates. Rocaglate-mediated inhibition of translation in C. auris activated a cell death program characterized by loss of mitochondrial membrane potential, increased caspase-like activity, and disrupted vacuolar homeostasis. In a rocaglate-sensitized C. albicans mutant engineered to exp...Continue Reading

References

May 2, 2002·Molecular Cell·Frank MadeoKai Uwe Fröhlich
Jul 26, 2002·Nature·Guri GiaeverMark Johnston
Sep 11, 2002·Progress in Nucleic Acid Research and Molecular Biology·George W RogersWilliam C Merrick
Jun 14, 2003·The Journal of Antimicrobial Chemotherapy·F C Odds
Nov 19, 2003·Proceedings of the National Academy of Sciences of the United States of America·Andrew J PhillipsMark Ramsdale
May 11, 2004·The Journal of Organic Chemistry·Bang Yeon HwangA Douglas Kinghorn
Jan 20, 2005·The Journal of Cell Biology·Andrei I PozniakovskyFedor F Severin
Apr 29, 2006·Science·Claire Veneault-FourreyNicholas J Talbot
Jul 28, 2006·The Journal of Physical Chemistry. a·Noël BoensJose M Alvarez-Pez
Aug 11, 2006·Molecular Biology of the Cell·Gabriela F RibeiroBjörn Johansson
Oct 13, 2006·Angewandte Chemie·Kimberly E BeattyDavid A Tirrell
Feb 26, 2008·Biochimica Et Biophysica Acta·Mark Ramsdale
Apr 19, 2008·Science·Maureen E HillenmeyerGuri Giaever
Jun 14, 2008·The Journal of Clinical Investigation·Marie-Eve BordeleauJerry Pelletier
Sep 19, 2008·Molecular Biology of the Cell·Margret RyanTom H Stevens
Apr 7, 2009·Biochimica Et Biophysica Acta·Eduardo Cebollero, Fulvio Reggiori
Apr 19, 2011·Proceedings of the National Academy of Sciences of the United States of America·Lauren E BrownJohn A Porco
Jun 8, 2011·Microbiology and Molecular Biology Reviews : MMBR·Rebecca S ShapiroLeah E Cowen
Jul 1, 2011·Journal of Clinical Microbiology·Wee Gyo LeeHee-Chang Jang
Nov 10, 2011·Molecular Systems Biology·Murat CokolFrederick P Roth
May 5, 2012·Microbiological Research·Irshad Ali KhanFu-Cheng Lin
Apr 26, 2013·ACS Chemical Biology·Heather SadlishN Rao Movva
Jul 20, 2014·Journal of Cell Science·A Pedro GonçalvesArnaldo Videira
Dec 21, 2014·Methods : a Companion to Methods in Enzymology·Elizabeth Delorme-AxfordDaniel J Klionsky
Jan 15, 2016·BMC Cancer·Wei-Lun ChenJoanna E Burdette
Jan 29, 2016·Scientific Reports·Fa-Liang AnLing-Yi Kong
Jul 2, 2016·Scientific Reports·Yann DesfougèresAndreas Mayer
Oct 26, 2016·Antimicrobial Resistance and Infection Control·Silke SchelenzMatthew C Fisher

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Citations

Dec 17, 2020·Antibiotics·Nicole Griffith, Larry Danziger
Mar 12, 2021·Wiley Interdisciplinary Reviews. RNA·J J David HoPhilip A Marsden
Mar 7, 2021·Journal of Fungi·Corey M KnowlesJohn C Panepinto
May 1, 2021·International Journal of Molecular Sciences·Lucia ČernákováCélia F Rodrigues
Jun 10, 2021·Phytochemistry Reviews : Proceedings of the Phytochemical Society of Europe·Harald Greger
Jun 29, 2021·Expert Review of Clinical Pharmacology·Daniele R GiacobbeMatteo Bassetti

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Methods Mentioned

BETA
Transmission electron microscopy
Fluorescence
xenograft

Software Mentioned

Java
CytExpert
TreeView
Clustal omega

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