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Open AccessCommunication

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

ICBAS-Instituto de Ciências Biomédicas Abel Salazar, University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal
Fungal Genetics Stock Center, Department of Plant Pathology, Kansas State University, 4024 Throckmorton Plant Sciences Center, Manhattan, KS 66506, USA
Department of Plant and Microbial Biology, University of California, Berkeley, CA 94720, USA
Environmental Genomics and Systems Biology Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, CA 94720, USA
i3S—Institute for Research and Innovation in Health, University of Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal
Author to whom correspondence should be addressed.
Present address: Institute of Molecular Biology, Academia Sinica, Taipei 11529, Taiwan.
Present address: Bolt Threads Inc., 5858 Horton St #400, Emeryville, CA 94608, USA.
J. Fungi 2019, 5(4), 114;
Received: 12 November 2019 / Revised: 4 December 2019 / Accepted: 4 December 2019 / Published: 6 December 2019
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. View Full-Text
Keywords: antimicrobial drug resistance; cell death; CZT-1; ABC-3; acriflavine; staurosporine antimicrobial drug resistance; cell death; CZT-1; ABC-3; acriflavine; staurosporine
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Gonçalves, A.P.; McCluskey, K.; Glass, N.L.; Videira, A. The Fungal Cell Death Regulator czt-1 Is Allelic to acr-3. J. Fungi 2019, 5, 114.

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