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Title: The Fungal Cell Death Regulator czt-1 Is Allelic to acr-3

Abstract

Fungal infections have far-reaching implications that range from severe human disease to a panoply of disruptive agricultural and ecological effects, making it imperative to identify and understand the molecular pathways governing the response to antifungal compounds. In this context, CZT-1 (cell death-activated zinc cluster transcription factor) functions as a master regulator of cell death and drug susceptibility in Neurospora crassa. Here we provide evidence indicating that czt-1 is allelic to acr-3, a previously described locus that we now found to harbor a point mutation in its coding sequence. This nonsynonymous amino acid substitution in a low complexity region of CZT-1/ACR-3 caused a robust gain-of-function that led to reduced sensitivity to acriflavine and staurosporine, and increased expression of the drug efflux pump abc-3. Thus, accumulating evidence shows that CZT-1 is an important broad regulator of the cellular response to various antifungal compounds that appear to share common molecular targets.

Authors:
ORCiD logo [1];  [2];  [3]; ORCiD logo [4]
  1. Univ. of Porto (Portugal). ICBAS---Instituto de Ciências Biomédicas Abel Salazar
  2. Kansas State Univ., Manhattan, KS (United States). Dept. of Plant Pathology. Fungal Genetics Stock Center
  3. Univ. of California, Berkeley, CA (United States). Dept. of Plant and Microbial Biology; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Environmental Genomics and Systems Biology Division
  4. Univ. of Porto (Portugal). ICBAS---Instituto de Ciências Biomédicas Abel Salazar; Univ. of Porto (Portugal). i3S--Inst. for Research and Innovation in Health
Publication Date:
Research Org.:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1628395
Grant/Contract Number:  
AC02-05CH11231
Resource Type:
Accepted Manuscript
Journal Name:
Journal of Fungi
Additional Journal Information:
Journal Volume: 5; Journal Issue: 4; Journal ID: ISSN 2309-608X
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; Microbiology; Mycology; antimicrobial drug resistance; cell death; CZT-1; ABC-3; acriflavine; staurosporine

Citation Formats

Gonçalves, A. Pedro, McCluskey, Kevin, Glass, N. Louise, and Videira, Arnaldo. The Fungal Cell Death Regulator czt-1 Is Allelic to acr-3. United States: N. p., 2019. Web. https://doi.org/10.3390/jof5040114.
Gonçalves, A. Pedro, McCluskey, Kevin, Glass, N. Louise, & Videira, Arnaldo. The Fungal Cell Death Regulator czt-1 Is Allelic to acr-3. United States. https://doi.org/10.3390/jof5040114
Gonçalves, A. Pedro, McCluskey, Kevin, Glass, N. Louise, and Videira, Arnaldo. Sun . "The Fungal Cell Death Regulator czt-1 Is Allelic to acr-3". United States. https://doi.org/10.3390/jof5040114. https://www.osti.gov/servlets/purl/1628395.
@article{osti_1628395,
title = {The Fungal Cell Death Regulator czt-1 Is Allelic to acr-3},
author = {Gonçalves, A. Pedro and McCluskey, Kevin and Glass, N. Louise and Videira, Arnaldo},
abstractNote = {Fungal infections have far-reaching implications that range from severe human disease to a panoply of disruptive agricultural and ecological effects, making it imperative to identify and understand the molecular pathways governing the response to antifungal compounds. In this context, CZT-1 (cell death-activated zinc cluster transcription factor) functions as a master regulator of cell death and drug susceptibility in Neurospora crassa. Here we provide evidence indicating that czt-1 is allelic to acr-3, a previously described locus that we now found to harbor a point mutation in its coding sequence. This nonsynonymous amino acid substitution in a low complexity region of CZT-1/ACR-3 caused a robust gain-of-function that led to reduced sensitivity to acriflavine and staurosporine, and increased expression of the drug efflux pump abc-3. Thus, accumulating evidence shows that CZT-1 is an important broad regulator of the cellular response to various antifungal compounds that appear to share common molecular targets.},
doi = {10.3390/jof5040114},
journal = {Journal of Fungi},
number = 4,
volume = 5,
place = {United States},
year = {2019},
month = {12}
}

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