Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

DNA Methylation on N6-Adenine Regulates the Hyphal Development During Dimorphism in the Early-Diverging Fungus Mucor lusitanicus

Macario Osorio-Concepción
ORCID logo ,
Carlos Lax
ORCID logo ,
Eusebio Navarro
ORCID logo ,
Francisco E. Nicolás
* ORCID logo ,
Victoriano Garre
* ORCID logo
Version 1 : Received: 22 July 2021 / Approved: 23 July 2021 / Online: 23 July 2021 (07:57:16 CEST)

A peer-reviewed article of this Preprint also exists.

Osorio-Concepción, M.; Lax, C.; Navarro, E.; Nicolás, F.E.; Garre, V. DNA Methylation on N6-Adenine Regulates the Hyphal Development during Dimorphism in the Early-Diverging Fungus Mucor lusitanicus. J. Fungi 2021, 7, 738. Osorio-Concepción, M.; Lax, C.; Navarro, E.; Nicolás, F.E.; Garre, V. DNA Methylation on N6-Adenine Regulates the Hyphal Development during Dimorphism in the Early-Diverging Fungus Mucor lusitanicus. J. Fungi 2021, 7, 738.

Abstract

The epigenetic modifications control the pathogenicity of human pathogenic fungi, which have been poorly studied in Mucorales; causative agents of mucormycosis. This order belongs to a group referred to as early-diverging fungi that are characterized by high levels of N6-methyldeoxyadenine (6mA) in their genome with dense 6mA clusters associated with actively expressed genes. AlkB enzymes can act as demethylases of 6mA in DNA, with the most remarkable eukaryotic examples being mammalian ALKBH1 and Caenorhabditis elegans NMAD-1. Mucor lusitanicus (formerly M. circinelloides f. lusitanicus) genome contains one gene, dmt1, and two genes, dmt2 and dmt3, encoding proteins homologs to C. elegans NMAD-1 and ALKBH1, respectively. The function of the three genes was analyzed by the generation of single and double deletion mutants for each gene. Multiple processes were studied in the mutants, but defects were only found in single and double deletion mutants for dmt1. In contrast to the wild-type strain, dmt1 mutants showed an increase of 6mA levels during the dimorphic transition, suggesting that 6mA regulates dimorphism in M. lusitanicus. Furthermore, the spores of dmt1 mutants challenged with macrophages underwent a reduction of polar growth, suggesting that 6mA also has a role during the spore-macrophage interaction that could be important in the infection process.

Keywords

Mucormycosis; AlkB; demethylase; virulence; dimorphism; protein kinase A; hyphae development; Mucor

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Download PDF Download Supplementary

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our Diversity statement.

Leave a public comment
Send a private comment to the author(s)
* All users must log in before leaving a comment
Views 0
Downloads 0
Comments 0
Metrics 0
Get PDF Supplementary Files Cite Share 0
Bookmark BibSonomy Mendeley Reddit Delicious
×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.