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Epigenetic Regulation of Fungal Virulence
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Epigenetic Regulation of Fungal Virulence

A special issue of Journal of Fungi (ISSN 2309-608X). This special issue belongs to the section "Fungal Genomics, Genetics and Molecular Biology".

Deadline for manuscript submissions: closed (30 April 2021) | Viewed by 17901

Special Issue Editors

Dr. Neeraj Chauhan

E-Mail Website
Guest Editor
Public Health Research Institute (PHRI), Department of Microbiology, Biochemistry and Molecular Genetics New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ, USA
Interests: candidiasis; antifungal drug resistance; chromatin; epigenetics; host-fungal interactions; fungal pathogenesis
Prof. Dr. Karl Kuchler

E-Mail Website
Co-Guest Editor
Max Perutz Labs Viennam, Center for Medical Biochemistry, Campus Vienna Biocenter, Medical University of Vienna, Dr. Bohr-Gasse 9/2, A-1030 Vienna, Austria
Interests: host-fungal interactions; innate/adaptive antifungal immunity; immune signaling; fungal pathogens; Candida spp.

Special Issue Information

Dear Colleagues,

Conrad Waddington conied the term “epigenetics” in 1942 to explain the presence of other mechanisms of inheritance of certain traits in addition to genetics. Since then, it has been shown that epigenetic changes such as chromatin remodeling involving histone acetylation and methylation play a critical role in the regulation of gene expression. New evidence indicates that chromatin structure impacts fungal virulence and/or pathogen fitness in the host. Furthermore, chromatin remodeling and assembly pathways regulate the dynamic interplay with host immune surveillance, facilitate immune evasion, and drive antifungal drug resistance.

During host-pathogen interactions, the host immune system often triggers epigenetic changes in the pathogen, which in turn activate transcriptional networks to coordinate an adaptive response. Conversely, it has also been noted that certain pathogens manipulate the post-translational modification of host proteins to promote their replication and to evade the host immune system.

To continue a discussion on the spirit of epigenetics and of the recent exciting discoveries in the field, we would like to dedicate a Special Issue to “Epigenetic regulation of fungal virulence.” Research articles that include, but are not limited to, current and emerging therapies targeting chromatin, phenotypes of fungal epigenetic (lysine acetyltransferases (KATs)/lysine deacetylases (KDACs) and methyltransferases) regulatory mutants, inhibitors of KATs/KDACs and methyltransferases, and antifungal drugs and their mechanism(s) of action will be of special interest.

Dr. Neeraj Chauhan
Prof. Dr. Karl Kuchler

Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Fungi is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Candida
  • Chromatin
  • Acetylation
  • Epigenetics
  • Methylation
  • Virulence

Published Papers (4 papers)

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Research

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19 pages, 4299 KiB  
Article
ATAC-Seq Identifies Chromatin Landscapes Linked to the Regulation of Oxidative Stress in the Human Fungal Pathogen Candida albicans
by Sabrina Jenull, Michael Tscherner, Theresia Mair and Karl Kuchler
J. Fungi 2020, 6(3), 182; https://0-doi-org.brum.beds.ac.uk/10.3390/jof6030182 - 21 Sep 2020
Cited by 13 | Viewed by 4910
Abstract
Human fungal pathogens often encounter fungicidal stress upon host invasion, but they can swiftly adapt by transcriptional reprogramming that enables pathogen survival. Fungal immune evasion is tightly connected to chromatin regulation. Hence, fungal chromatin modifiers pose alternative treatment options to combat fungal infections. [...] Read more.
Human fungal pathogens often encounter fungicidal stress upon host invasion, but they can swiftly adapt by transcriptional reprogramming that enables pathogen survival. Fungal immune evasion is tightly connected to chromatin regulation. Hence, fungal chromatin modifiers pose alternative treatment options to combat fungal infections. Here, we present an assay for transposase-accessible chromatin using sequencing (ATAC-seq) protocol adapted for the opportunistic pathogen Candida albicans to gain further insight into the interplay of chromatin accessibility and gene expression mounted during fungal adaptation to oxidative stress. The ATAC-seq workflow not only facilitates the robust detection of genomic regions with accessible chromatin but also allows for the precise modeling of nucleosome positions in C. albicans. Importantly, the data reveal genes with altered chromatin accessibility in upstream regulatory regions, which correlate with transcriptional regulation during oxidative stress. Interestingly, many genes show increased chromatin accessibility without change in gene expression upon stress exposure. Such chromatin signatures could predict yet unknown regulatory factors under highly dynamic transcriptional control. Additionally, de novo motif analysis in genomic regions with increased chromatin accessibility upon H2O2 treatment shows significant enrichment for Cap1 binding sites, a major factor of oxidative stress responses in C. albicans. Taken together, the ATAC-seq workflow enables the identification of chromatin signatures and highlights the dynamics of regulatory mechanisms mediating environmental adaptation of C. albicans. Full article
(This article belongs to the Special Issue Epigenetic Regulation of Fungal Virulence)
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Review

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24 pages, 1215 KiB  
Review
The Roles of Chromatin Accessibility in Regulating the Candida albicans White-Opaque Phenotypic Switch
by Mohammad N. Qasim, Ashley Valle Arevalo, Clarissa J. Nobile and Aaron D. Hernday
J. Fungi 2021, 7(1), 37; https://0-doi-org.brum.beds.ac.uk/10.3390/jof7010037 - 09 Jan 2021
Cited by 6 | Viewed by 3541
Abstract
Candida albicans, a diploid polymorphic fungus, has evolved a unique heritable epigenetic program that enables reversible phenotypic switching between two cell types, referred to as “white” and “opaque”. These cell types are established and maintained by distinct transcriptional programs that lead to [...] Read more.
Candida albicans, a diploid polymorphic fungus, has evolved a unique heritable epigenetic program that enables reversible phenotypic switching between two cell types, referred to as “white” and “opaque”. These cell types are established and maintained by distinct transcriptional programs that lead to differences in metabolic preferences, mating competencies, cellular morphologies, responses to environmental signals, interactions with the host innate immune system, and expression of approximately 20% of genes in the genome. Transcription factors (defined as sequence specific DNA-binding proteins) that regulate the establishment and heritable maintenance of the white and opaque cell types have been a primary focus of investigation in the field; however, other factors that impact chromatin accessibility, such as histone modifying enzymes, chromatin remodelers, and histone chaperone complexes, also modulate the dynamics of the white-opaque switch and have been much less studied to date. Overall, the white-opaque switch represents an attractive and relatively “simple” model system for understanding the logic and regulatory mechanisms by which heritable cell fate decisions are determined in higher eukaryotes. Here we review recent discoveries on the roles of chromatin accessibility in regulating the C. albicans white-opaque phenotypic switch. Full article
(This article belongs to the Special Issue Epigenetic Regulation of Fungal Virulence)
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24 pages, 1748 KiB  
Review
Chromatin Structure and Drug Resistance in Candida spp.
by Callum J. O’Kane, Rachel Weild and Edel M. Hyland
J. Fungi 2020, 6(3), 121; https://0-doi-org.brum.beds.ac.uk/10.3390/jof6030121 - 30 Jul 2020
Cited by 8 | Viewed by 3986
Abstract
Anti-microbial resistance (AMR) is currently one of the most serious threats to global human health and, appropriately, research to tackle AMR garnishes significant investment and extensive attention from the scientific community. However, most of this effort focuses on antibiotics, and research into anti-fungal [...] Read more.
Anti-microbial resistance (AMR) is currently one of the most serious threats to global human health and, appropriately, research to tackle AMR garnishes significant investment and extensive attention from the scientific community. However, most of this effort focuses on antibiotics, and research into anti-fungal resistance (AFR) is vastly under-represented in comparison. Given the growing number of vulnerable, immunocompromised individuals, as well as the positive impact global warming has on fungal growth, there is an immediate urgency to tackle fungal disease, and the disturbing rise in AFR. Chromatin structure and gene expression regulation play pivotal roles in the adaptation of fungal species to anti-fungal stress, suggesting a potential therapeutic avenue to tackle AFR. In this review we discuss both the genetic and epigenetic mechanisms by which chromatin structure can dictate AFR mechanisms and will present evidence of how pathogenic yeast, specifically from the Candida genus, modify chromatin structure to promote survival in the presence of anti-fungal drugs. We also discuss the mechanisms by which anti-chromatin therapy, specifically lysine deacetylase inhibitors, influence the acquisition and phenotypic expression of AFR in Candida spp. and their potential as effective adjuvants to mitigate against AFR. Full article
(This article belongs to the Special Issue Epigenetic Regulation of Fungal Virulence)
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19 pages, 1907 KiB  
Review
SUMOylation in Human Pathogenic Fungi: Role in Physiology and Virulence
by Mahima Sagar Sahu, Sandip Patra, Kundan Kumar and Rupinder Kaur
J. Fungi 2020, 6(1), 32; https://0-doi-org.brum.beds.ac.uk/10.3390/jof6010032 - 04 Mar 2020
Cited by 9 | Viewed by 4492
Abstract
The small ubiquitin-related modifier (SUMO) protein is an important component of the post-translational protein modification systems in eukaryotic cells. It is known to modify hundreds of proteins involved in diverse cellular processes, ranging from nuclear pore dynamics to signal transduction pathways. Owing to [...] Read more.
The small ubiquitin-related modifier (SUMO) protein is an important component of the post-translational protein modification systems in eukaryotic cells. It is known to modify hundreds of proteins involved in diverse cellular processes, ranging from nuclear pore dynamics to signal transduction pathways. Owing to its reversible nature, the SUMO-conjugation of proteins (SUMOylation) holds a prominent place among mechanisms that regulate the functions of a wide array of cellular proteins. The dysfunctional SUMOylation system has been associated with many human diseases, including neurodegenerative and autoimmune disorders. Furthermore, the non-pathogenic yeast Saccharomyces cerevisiae has served as an excellent model to advance our understanding of enzymes involved in SUMOylation and proteins modified by SUMOylation. Taking advantage of the tools and knowledge obtained from the S. cerevisiae SUMOylation system, research on fungal SUMOylation is beginning to gather pace, and new insights into the role of SUMOylation in the pathobiology of medically important fungi are emerging. Here, we summarize the known information on components of the SUMOylation machinery, and consequences of overexpression or deletion of these components in the human pathogenic fungi, with major focus on two prevalent Candida bloodstream pathogens, C. albicans and C. glabrata. Additionally, we have identified SUMOylation components, through in silico analysis, in four medically relevant fungi, and compared their sequence similarity with S. cerevisiae counterparts. SUMOylation modulates the virulence of C. albicans and C. glabrata, while it is required for conidia production in Aspergillus nidulans and A. flavus. In addition to highlighting these recent developments, we discuss how SUMOylation fine tunes the expression of virulence factors, and influences survival of fungal cells under diverse stresses in vitro and in the mammalian host. Full article
(This article belongs to the Special Issue Epigenetic Regulation of Fungal Virulence)
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