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A Mucoralean White Collar-1 Photoreceptor Controls Virulence by Regulating an Intricate Gene Network during Host Interactions

Departmento de Genética y Microbiología, Facultad de Biología, Universidad de Murcia, 30100 Murcia, Spain
Unidad de Microbiología, Universitat Rovira i Virgili, IISPV, 43003 Tarragona, Spain
Authors to whom correspondence should be addressed.
First authorship.
Academic Editor: Maria Salomé Gomes
Microorganisms 2021, 9(2), 459;
Received: 30 December 2020 / Revised: 8 February 2021 / Accepted: 18 February 2021 / Published: 23 February 2021
(This article belongs to the Special Issue From Host-Pathogen Interaction to Host-Directed Therapies)
Mucolares are an ancient group of fungi encompassing the causal agents for the lethal infection mucormycosis. The high lethality rates, the emerging character of this disease, and the broad antifungal resistance of its causal agents are mucormycosis features that are alarming clinicians and researchers. Thus, the research field around mucormycosis is currently focused on finding specific weaknesses and targets in Mucorales for developing new treatments. In this work, we tested the role of the white-collar genes family in the virulence potential of Mucor lusitanicus. Study of the three genes of this family, mcwc-1a, mcwc-1b, and mcwc-1c, resulted in a marked functional specialization, as only mcwc-1a was essential to maintain the virulence potential of M. lusitanicus. The traditional role of wc-1 genes regulating light-dependent responses is a thoroughly studied field, whereas their role in virulence remains uncharacterized. In this work, we investigated the mechanism involving mcwc-1a in virulence from an integrated transcriptomic and functional approach during the host–pathogen interaction. Our results revealed mcwc-1a as a master regulator controlling an extensive gene network. Further dissection of this gene network clustering its components by type of regulation and functional criteria disclosed a multifunctional mechanism depending on diverse pathways. In the absence of phagocytic cells, mcwc-1a controlled pathways related to cell motility and the cytoskeleton that could be associated with the essential tropism during tissue invasion. After phagocytosis, several oxidative response pathways dependent on mcwc-1a were activated during the germination of M. lusitanicus spores inside phagocytic cells, which is the first stage of the infection. The third relevant group of genes involved in virulence and regulated by mcwc-1a belonged to the “unknown function,” indicating that new and hidden pathways are involved in virulence. The unknown function category is especially pertinent in the study of mucormycosis, as it is highly enriched in specific fungal genes that represent the most promising targets for developing new antifungal compounds. These results unveil a complex multifunctional mechanism used by wc-1 genes to regulate the pathogenic potential in Mucorales that could also apply to other fungal pathogens. View Full-Text
Keywords: white collar; mucormycosis; virulence; Mucorales; Mucor lusitanicus white collar; mucormycosis; virulence; Mucorales; Mucor lusitanicus
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MDPI and ACS Style

Pérez-Arques, C.; Navarro-Mendoza, M.I.; Murcia, L.; Lax, C.; Sanchis, M.; Capilla, J.; Navarro, E.; Garre, V.; Nicolás, F.E. A Mucoralean White Collar-1 Photoreceptor Controls Virulence by Regulating an Intricate Gene Network during Host Interactions. Microorganisms 2021, 9, 459.

AMA Style

Pérez-Arques C, Navarro-Mendoza MI, Murcia L, Lax C, Sanchis M, Capilla J, Navarro E, Garre V, Nicolás FE. A Mucoralean White Collar-1 Photoreceptor Controls Virulence by Regulating an Intricate Gene Network during Host Interactions. Microorganisms. 2021; 9(2):459.

Chicago/Turabian Style

Pérez-Arques, Carlos, María Isabel Navarro-Mendoza, Laura Murcia, Carlos Lax, Marta Sanchis, Javier Capilla, Eusebio Navarro, Victoriano Garre, and Francisco Esteban Nicolás. 2021. "A Mucoralean White Collar-1 Photoreceptor Controls Virulence by Regulating an Intricate Gene Network during Host Interactions" Microorganisms 9, no. 2: 459.

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