Abstract
Mucormycosis is a lethal and difficult-to-treat fungal infection caused by fungi of the order Mucorales. Mucor lusitanicus, a member of Mucorales, is commonly used as a model to understand disease pathogenesis. However, transcriptional control of hyphal growth and virulence in Mucorales is poorly understood. This study aimed to investigate the role of Tec proteins, which belong to the TEA/ATTS transcription factor family, in the hyphal development and virulence of M. lusitanicus. Unlike in the genome of Ascomycetes and Basidiomycetes, which have a single Tec homologue, in the genome of Mucorales, two Tec homologues, Tec1 and Tec2, were found, except in that of Phycomyces blakesleeanus, with only one Tec homologue. tec1 and tec2 overexpression in M. lusitanicus increased mycelial growth, mitochondrial content and activity, expression of the rhizoferrin synthetase-encoding gene rfs, and virulence in nematodes and wax moth larvae but decreased cAMP levels and protein kinase A (PKA) activity. Furthermore, tec1- and tec2-overexpressing strains required adequate mitochondrial metabolism to promote the virulent phenotype. The heterotrimeric G beta subunit 1-encoding gene deletant strain (Δgpb1) increased cAMP-PKA activity, downregulation of both tec genes, decreased both virulence and hyphal development, but tec1 and tec2 overexpression restored these defects. Overexpression of allele-mutated variants of Tec1(S332A) and Tec2(S168A) in the putative phosphorylation sites for PKA increased both virulence and hyphal growth of Δgpb1. These findings suggest that Tec homologues promote mycelial development and virulence by enhancing mitochondrial metabolism and rhizoferrin accumulation, providing new information for the rational control of the virulent phenotype of M. lusitanicus.
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The data or strains generated or analyzed during this study are available from the corresponding author on reasonable request.
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We would like to thank to the Coordinación de la Investigación Científica de la Universidad Michoacana de San Nicolás de Hidalgo for their funding of this work (Grant number 2.36). V. A-C. and J.A. P-M. were postgraduate students supported by CONAHCyT scholarships. We would like to express our gratitude to the Laboratorio Estatal de Salud Pública del Estado de Michoacán, Secretaría de Salud de Michoacán for providing technical support.
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Conceptualization: VM-C. Supervision: VM-C. Methodology: VA-C, JAP-M, MIV-M, AG, RO-A, KVC-C, JR-E, MIR-D, SCL and VG. Writing—original draft preparation: VM-C. Writing—review and editing: VA-C, JAP-M, MIV-M, KVC-C, JR-E, MIR-D, SCL, VG, and VM-C. All authors have read and agreed to the published version of the manuscript.
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Alejandre-Castañeda, V., Patiño-Medina, J.A., Valle-Maldonado, M.I. et al. Transcription Factors Tec1 and Tec2 Play Key Roles in the Hyphal Growth and Virulence of Mucor lusitanicus Through Increased Mitochondrial Oxidative Metabolism. J Microbiol. 61, 1043–1062 (2023). https://doi.org/10.1007/s12275-023-00096-8
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DOI: https://doi.org/10.1007/s12275-023-00096-8