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Candida albicans targets that potentially synergize with fluconazole.

Author(s): Lu H, Shrivastava M, Whiteway M, Jiang Y

Fluconazole has characteristics that make it widely used in the clinical treatment of C. albicans infections. However, fluconazole has only a fungistatic activity in C. albicans, therefore, in the long-term treatment of C. albicans infection with fluconazol...

Article GUID: 33587857
Loss of Arp1, a putative actin-related protein, triggers filamentous and invasive growth and impairs pathogenicity in Candida albicans.

Author(s): Yao S, Feng Y, Islam A, Shrivastava M, Gu H, Lu Y, Sheng J, Whiteway M, Feng J

The polymorphous cellular shape of Candida albicans, in particular the transition from a yeast to a filamentous form, is crucial for either commensalism or life-threatening infections of the host. Various external or internal stimuli, including serum and nu...

Article GUID: 33363697
Nucleotide Excision Repair Protein Rad23 Regulates Cell Virulence Independent of Rad4 in Candida albicans.

Author(s): Feng J, Yao S, Dong Y, Hu J, Whiteway M, Feng J

mSphere. 2020 Feb 19;5(1): Authors: Feng J, Yao S, Dong Y, Hu J, Whiteway M, Feng J

Article GUID: 32075883
Hof1 plays a checkpoint related role in MMS induced DNA damage response in Candida albicans.

Author(s): Feng J, Islam A, Bean B, Feng J, Sparapani S, Shrivastava M, Goyal A, Omran RP, Mallick J, Whiteway M

Mol Biol Cell. 2020 Jan 15;:mbcE19060316 Authors: Feng J, Islam A, Bean B, Feng J, Sparapani S, Shrivastava M, Goyal A, Omran RP, Mallick J, Whiteway M

Article GUID: 31940254
RNA sequencing reveals an additional Crz1-binding motif in promoters of its target genes in the human fungal pathogen Candida albicans.

Author(s): Xu H, Fang T, Omran RP, Whiteway M, Jiang L

Cell Commun Signal. 2020 Jan 03;18(1):1 Authors: Xu H, Fang T, Omran RP, Whiteway M, Jiang L

Article GUID: 31900175
Screening of Candida albicans GRACE library revealed a unique pattern of biofilm formation under repression of the essential gene ILS1.

Author(s): Costa ACBP, Omran RP, Correia-Mesquita TO, Dumeaux V, Whiteway M

Sci Rep. 2019 Jun 24;9(1):9187 Authors: Costa ACBP, Omran RP, Correia-Mesquita TO, Dumeaux V, Whiteway M

Article GUID: 31235750
The Genomic Landscape of the Fungus-Specific SWI/SNF Complex Subunit, Snf6, in Candida albicans.

Author(s): Tebbji F, Chen Y, Sellam A, Whiteway M

mSphere. 2017 Nov-Dec;2(6): Authors: Tebbji F, Chen Y, Sellam A, Whiteway M

Article GUID: 29152582
Chemogenomic Profiling of the Fungal Pathogen Candida albicans.

Author(s): Chen Y, Mallick J, Maqnas A, Sun Y, Choudhury BI, Côte P, Yan L, Ni TJ, Li Y, Zhang D, Rodríguez-Ortiz R, Lv QZ, Jiang YY, Whiteway M

Antimicrob Agents Chemother. 2018 02;62(2): Authors: Chen Y, Mallick J, Maqnas A, Sun Y, Choudhury BI, Côte P, Yan L, Ni TJ, Li Y, Zhang D, Rodríguez-Ortiz R, Lv QZ, Jiang YY, Whiteway M

Article GUID: 29203491
Epigenetic control of pheromone MAPK signaling determines sexual fecundity in Candida albicans.

Author(s): Scaduto CM, Kabrawala S, Thomson GJ, Scheving W, Ly A, Anderson MZ, Whiteway M, Bennett RJ

Proc Natl Acad Sci U S A. 2017 12 26;114(52):13780-13785 Authors: Scaduto CM, Kabrawala S, Thomson GJ, Scheving W, Ly A, Anderson MZ, Whiteway M, Bennett RJ

Article GUID: 29255038
Evolutionary Transition of GAL Regulatory Circuit from Generalist to Specialist Function in Ascomycetes.

Author(s): Choudhury BI, Whiteway M

Trends Microbiol. 2018 08;26(8):692-702 Authors: Choudhury BI, Whiteway M

Article GUID: 29395731
Erratum for Chen et al., "Chemogenomic Profiling of the Fungal Pathogen Candida albicans".

Author(s): Chen Y, Mallick J, Maqnas A, Sun Y, Choudhury BI, Côte P, Yan L, Ni TJ, Li Y, Zhang D, Rodríguez-Ortiz R, Lv QZ, Jiang YY, Whiteway M...

Antimicrob Agents Chemother. 2018 04;62(4): Authors: Chen Y, Mallick J, Maqnas A, Sun Y, Choudhury BI, Côte P, Yan L, Ni TJ, Li Y, Zhang D, Rodríguez-Ortiz R, Lv QZ, Jiang YY, Whiteway M...

Article GUID: 29588354
Tuning Hsf1 levels drives distinct fungal morphogenetic programs with depletion impairing Hsp90 function and overexpression expanding the target space.

Author(s): 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

PLoS Genet. 2018 03;14(3):e1007270 Authors: 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

Article GUID: 29590106
Functional divergence of a global regulatory complex governing fungal filamentation.

Author(s): 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...

Functional divergence of a global regulatory complex governing fungal filamentation.

PLoS Genet. 2019 01;15(1):e1007901

Authors: Polvi EJ, Veri AO, Liu Z, Hossain S, Hyde S, Kim...

Article GUID: 30615616
The adaptor protein Ste50 directly modulates yeast MAPK signaling specificity through differential connections of its RA domain.

Author(s): Sharmeen N, Sulea T, Whiteway M, Wu C

Mol Biol Cell. 2019 03 15;30(6):794-807 Authors: Sharmeen N, Sulea T, Whiteway M, Wu C

Article GUID: 30650049
MAP Kinase Regulation of the Candida albicans Pheromone Pathway.

Author(s): Rastghalam G, Omran RP, Alizadeh M, Fulton D, Mallick J, Whiteway M

mSphere. 2019 02 20;4(1): Authors: Rastghalam G, Omran RP, Alizadeh M, Fulton D, Mallick J, Whiteway M

Article GUID: 30787119
The evolutionary rewiring of the ribosomal protein transcription pathway modifies the interaction of transcription factor heteromer Ifh1-Fhl1 (interacts with forkhead 1-forkhead-like 1) with the DNA-binding specificity element.

Author(s): Mallick J, Whiteway M

J Biol Chem. 2013 Jun 14;288(24):17508-19 Authors: Mallick J, Whiteway M

Article GUID: 23625919
The tricarboxylic acid cycle, cell wall integrity pathway, cytokinesis and intracellular pH homeostasis are involved in the sensitivity of Candida albicans cells to high levels of extracellular calcium.

Author(s): Xu H, Whiteway M, Jiang L

Genomics. 2018 Aug 10;: Authors: Xu H, Whiteway M, Jiang L

Article GUID: 30102968
Mms21: A Putative SUMO E3 Ligase in Candida albicans That Negatively Regulates Invasiveness and Filamentation, and Is Required for the Genotoxic and Cellular Stress Response.

Author(s): Islam A, Tebbji F, Mallick J, Regan H, Dumeaux V, Omran RP, Whiteway M

Genetics. 2019 02;211(2):579-595 Authors: Islam A, Tebbji F, Mallick J, Regan H, Dumeaux V, Omran RP, Whiteway M

Article GUID: 30530734
Rewiring of the Ppr1 Zinc Cluster Transcription Factor from Purine Catabolism to Pyrimidine Biogenesis in the Saccharomycetaceae.

Author(s): Tebung WA, Choudhury BI, Tebbji F, Morschhäuser J, Whiteway M

Curr Biol. 2016 07 11;26(13):1677-1687 Authors: Tebung WA, Choudhury BI, Tebbji F, Morschhäuser J, Whiteway M

Article GUID: 27321996
Beauvericin Potentiates Azole Activity via Inhibition of Multidrug Efflux, Blocks Candida albicans Morphogenesis, and Is Effluxed via Yor1 and Circuitry Controlled by Zcf29.

Author(s): Shekhar-Guturja T, Tebung WA, Mount H, Liu N, Köhler JR, Whiteway M, Cowen LE

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

Article GUID: 27736764
Put3 Positively Regulates Proline Utilization in Candida albicans.

Author(s): Tebung WA, Omran RP, Fulton DL, Morschhäuser J, Whiteway M

mSphere. 2017 Nov-Dec;2(6): Authors: Tebung WA, Omran RP, Fulton DL, Morschhäuser J, Whiteway M

Article GUID: 29242833
Cinnamomum zeylanicum bark essential oil induces cell wall remodelling and spindle defects in Candida albicans.

Author(s): Shahina Z, El-Ganiny AM, Minion J, Whiteway M, Sultana T, Dahms TES

Fungal Biol Biotechnol. 2018;5:3 Authors: Shahina Z, El-Ganiny AM, Minion J, Whiteway M, Sultana T, Dahms TES

Article GUID: 29456868
Title:Tuning Hsf1 levels drives distinct fungal morphogenetic programs with depletion impairing Hsp90 function and overexpression expanding the target space.
Authors: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
Link:https://www.ncbi.nlm.nih.gov/pubmed/29590106?dopt=Abstract
DOI:10.1371/journal.pgen.1007270
Category:PLoS Genet
PMID:29590106
Dept Affiliation: BIOLOGY
1 Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
2 Faculty of Health Sciences, University of Macau, Macau SAR, China.
3 Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario, Canada.
4 Infectious Disease Research Centre, Université Laval, Quebec City, Quebec, Canada.
5 Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
6 Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, United States of America.
7 Department of Biology, Concordia University, Montréal, Quebec, Canada.

Description:

Tuning Hsf1 levels drives distinct fungal morphogenetic programs with depletion impairing Hsp90 function and overexpression expanding the target space.

PLoS Genet. 2018 03;14(3):e1007270

Authors: 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

Abstract

The capacity to respond to temperature fluctuations is critical for microorganisms to survive within mammalian hosts, and temperature modulates virulence traits of diverse pathogens. One key temperature-dependent virulence trait of the fungal pathogen Candida albicans is its ability to transition from yeast to filamentous growth, which is induced by environmental cues at host physiological temperature. A key regulator of temperature-dependent morphogenesis is the molecular chaperone Hsp90, which has complex functional relationships with the transcription factor Hsf1. Although Hsf1 controls global transcriptional remodeling in response to heat shock, its impact on morphogenesis remains unknown. Here, we establish an intriguing paradigm whereby overexpression or depletion of C. albicans HSF1 induces morphogenesis in the absence of external cues. HSF1 depletion compromises Hsp90 function, thereby driving filamentation. HSF1 overexpression does not impact Hsp90 function, but rather induces a dose-dependent expansion of Hsf1 direct targets that drives overexpression of positive regulators of filamentation, including Brg1 and Ume6, thereby bypassing the requirement for elevated temperature during morphogenesis. This work provides new insight into Hsf1-mediated environmentally contingent transcriptional control, implicates Hsf1 in regulation of a key virulence trait, and highlights fascinating biology whereby either overexpression or depletion of a single cellular regulator induces a profound developmental transition.

PMID: 29590106 [PubMed - indexed for MEDLINE]