- Transcription Factors Tec1 and Tec2 Play Key Roles in the Hyphal Growth and Virulence of Mucor lusitanicus Through Increased Mitochondrial Oxidative Metabolism
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Viridiana Alejandre-Castañeda , J. Alberto Patiño-Medina , Marco I. Valle-Maldonado , Alexis García , Rafael Ortiz-Alvarado , León F. Ruíz-Herrera , Karla Viridiana Castro-Cerritos , Joel Ramírez-Emiliano , Martha I. Ramírez-Díaz , Victoriano Garre , Soo Chan Lee , Víctor Meza-Carmen
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J. Microbiol. 2023;61(12):1043-1062. Published online December 19, 2023
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DOI: https://doi.org/10.1007/s12275-023-00096-8
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Correction in: J. Microbiol 2025;63(4):e2504100
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 Abstract
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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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Citations
Citations to this article as recorded by  - Heterotrimeric G-gamma 1 (Gpg1) participates with G-beta 1 (Gpb1) in the induction of hyphal growth and virulence via the PKA pathway in Mucor lusitanicus
J. Alberto Patiño-Medina, David Vargas-Tejeda, Nancy Y. Reyes-Mares, Viridiana Alejandre-Castañeda, Cesar J. Torres-Cortes, Carlos Pérez-Arques, Leon F. Ruiz-Herrera, Joel Ramírez-Emiliano, Sandeep Vellanki, Marco I. Valle-Maldonado, Karla Viridiana Castr
Fungal Genetics and Biology.2025; 178: 103974. CrossRef - A one-pot five component reaction for the synthesis of tetrazol-benzofuran hybrids and their inhibitory activity against Mucor lusitanicus
Cesia M. Aguilar-Morales, Viridiana Alejandre-Castañeda, Claudia Contreras-Celedón, Martha Isela Ramírez-Díaz, Alejandro Islas-Jácome, Victor Meza-Carmen, Luis Chacón-García, Carlos J. Cortés-García
Organic & Biomolecular Chemistry.2024; 22(35): 7240. CrossRef -
Functional characterization of two survival factor 1 genes in
Mucor lusitanicus
Olivér Jáger, Csilla Szebenyi, Tammam Khaliefeh Siliman Abu Saleem, Anna Molnár, Vanda Kovács, Karina Kiss, Mónika Homa, Bernadett Vágó, Sándor Kiss-Vetráb, Mónika Varga, Rita Sinka, Csaba Vágvölgyi, Gábor Nagy, Tamás Papp, Renato Kovacs
Microbiology Spectrum.2024;[Epub] CrossRef
- Gastrointestinal microbiota alteration induced by Mucor circinelloides in a murine model
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Katherine D. Mueller , Hao Zhang , Christian R. Serrano , R. Blake Billmyre , Eun Young Huh , Philipp Wiemann , Nancy P. Keller , Yufeng Wang , Joseph Heitman , Soo Chan Lee
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J. Microbiol. 2019;57(6):509-520. Published online May 27, 2019
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DOI: https://doi.org/10.1007/s12275-019-8682-x
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Abstract
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Mucor circinelloides is a pathogenic fungus and etiologic agent
of mucormycosis. In 2013, cases of gastrointestinal illness
after yogurt consumption were reported to the US FDA, and
the producer found that its products were contaminated with
Mucor. A previous study found that the Mucor strain isolated
from an open contaminated yogurt exhibited virulence
in a murine systemic infection model and showed that this
strain is capable of surviving passage through the gastrointestinal
tract of mice. In this study, we isolated another Mucor
strain from an unopened yogurt that is closely related but
distinct from the first Mucor strain and subsequently examined
if Mucor alters the gut microbiota in a murine host
model. DNA extracted from a ten-day course of stool samples
was used to analyze the microbiota in the gastrointestinal
tracts of mice exposed via ingestion of Mucor spores. The
bacterial 16S rRNA gene and fungal ITS1 sequences obtained
were used to identify taxa of each kingdom. Linear regressions
revealed that there are changes in bacterial and fungal abundance
in the gastrointestinal tracts of mice which ingested
Mucor. Furthermore, we found an increased abundance of
the bacterial genus Bacteroides and a decreased abundance
of the bacteria Akkermansia muciniphila in the gastrointestinal
tracts of exposed mice. Measurements of abundances
show shifts in relative levels of multiple bacterial and fungal
taxa between mouse groups. These findings suggest that exposure
of the gastrointestinal tract to Mucor can alter the microbiota
and, more importantly, illustrate an interaction between
the intestinal mycobiota and bacteriota. In addition, Mucor was able to induce increased permeability in epithelial
cell monolayers in vitro, which might be indicative of unstable
intestinal barriers. Understanding how the gut microbiota is
shaped is important to understand the basis of potential methods
of treatment for gastrointestinal illness. How the gut
microbiota changes in response to exposure, even by pathogens
not considered to be causative agents of food-borne illness,
may be important to how commercial food producers
prevent and respond to contamination of products aimed at
the public. This study provides evidence that the fungal microbiota,
though understudied, may play an important role
in diseases of the human gut.
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