scholarly journals Multicopper Oxidases in Saccharomyces cerevisiae and Human Pathogenic Fungi

2020 ◽  
Vol 6 (2) ◽  
pp. 56
Author(s):  
Tanmoy Chakraborty ◽  
Renáta Tóth ◽  
Joshua D. Nosanchuk ◽  
Attila Gácser
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Environmental Conditions ◽  
Defense Mechanisms ◽  
Fungal Pathogens ◽  
Lignin Degradation ◽  
Pathogenic Fungi ◽  
Fungal Species ◽  
Multicopper Oxidases ◽  
Fungal Virulence ◽  
Physiological Processes

Multicopper oxidases (MCOs) are produced by microscopic and macroscopic fungal species and are involved in various physiological processes such as morphogenesis, lignin degradation, and defense mechanisms to stress inducing environmental conditions as well as fungal virulence. This review will summarize our current understanding regarding the functions of MCOs present in Saccharomyces cerevisiae and in different human fungal pathogens. Of the two main MCO groups, the first group of MCOs is involved in iron homoeostasis and the second includes laccases. This review will also discuss their role in the pathogenesis of human fungal pathogens.

scholarly journals Mitotic Recombination and Adaptive Genomic Changes in Human Pathogenic Fungi

Genes ◽  
2019 ◽  
Vol 10 (11) ◽  
pp. 901 ◽  
Author(s):  
Asiya Gusa ◽  
Sue Jinks-Robertson
Keyword(s):  
Fungal Pathogens ◽  
Repetitive Sequences ◽  
Pathogenic Fungi ◽  
Genetic Alterations ◽  
Fungal Species ◽  
Chronic Infections ◽  
Yeast Saccharomyces Cerevisiae ◽  
Genomic Changes ◽  
Break Site ◽  
Repair Mechanisms

Genome rearrangements and ploidy alterations are important for adaptive change in the pathogenic fungal species Candida and Cryptococcus, which propagate primarily through clonal, asexual reproduction. These changes can occur during mitotic growth and lead to enhanced virulence, drug resistance, and persistence in chronic infections. Examples of microevolution during the course of infection were described in both human infections and mouse models. Recent discoveries defining the role of sexual, parasexual, and unisexual cycles in the evolution of these pathogenic fungi further expanded our understanding of the diversity found in and between species. During mitotic growth, damage to DNA in the form of double-strand breaks (DSBs) is repaired, and genome integrity is restored by the homologous recombination and non-homologous end-joining pathways. In addition to faithful repair, these pathways can introduce minor sequence alterations at the break site or lead to more extensive genetic alterations that include loss of heterozygosity, inversions, duplications, deletions, and translocations. In particular, the prevalence of repetitive sequences in fungal genomes provides opportunities for structural rearrangements to be generated by non-allelic (ectopic) recombination. In this review, we describe DSB repair mechanisms and the types of resulting genome alterations that were documented in the model yeast Saccharomyces cerevisiae. The relevance of similar recombination events to stress- and drug-related adaptations and in generating species diversity are discussed for the human fungal pathogens Candida albicans and Cryptococcus neoformans.

scholarly journals The Ustilago hordei–Barley Interaction is a Versatile System for Characterization of Fungal Effectors

2021 ◽  
Vol 7 (2) ◽  
pp. 86
Author(s):  
Bilal Ökmen ◽  
Daniela Schwammbach ◽  
Guus Bakkeren ◽  
Ulla Neumann ◽  
Gunther Doehlemann
Keyword(s):  
Fungal Pathogens ◽  
Plant Pathogens ◽  
Expression System ◽  
Pathogenic Fungi ◽  
Effector Proteins ◽  
Mating Partner ◽  
Fungal Virulence ◽  
Functional Studies ◽  
Infection Structures ◽  
Ustilago Hordei

Obligate biotrophic fungal pathogens, such as Blumeria graminis and Puccinia graminis, are amongst the most devastating plant pathogens, causing dramatic yield losses in many economically important crops worldwide. However, a lack of reliable tools for the efficient genetic transformation has hampered studies into the molecular basis of their virulence or pathogenicity. In this study, we present the Ustilago hordei–barley pathosystem as a model to characterize effectors from different plant pathogenic fungi. We generate U. hordei solopathogenic strains, which form infectious filaments without the presence of a compatible mating partner. Solopathogenic strains are suitable for heterologous expression system for fungal virulence factors. A highly efficient Crispr/Cas9 gene editing system is made available for U. hordei. In addition, U. hordei infection structures during barley colonization are analyzed using transmission electron microscopy, showing that U. hordei forms intracellular infection structures sharing high similarity to haustoria formed by obligate rust and powdery mildew fungi. Thus, U. hordei has high potential as a fungal expression platform for functional studies of heterologous effector proteins in barley.

Virulence and in vitro Characteristics of Pathogenic Fungi Isolated from Soil by Baiting with Coptotermes formosanus (Isoptera: Rhinotermitidae)

2003 ◽  
Vol 38 (3) ◽  
pp. 342-358 ◽  
Author(s):  
Jianzhong Sun ◽  
James R. Fuxa ◽  
Gregg Henderson
Keyword(s):  
Pathogenic Fungi ◽  
Fungal Species ◽  
Coptotermes Formosanus ◽  
Survival Times ◽  
Fungal Virulence ◽  
Fungal Isolates ◽  
Sampling Locations ◽  
Lethal Doses

Coptotermes formosanus Shiraki (Isoptera: Rhinotermitidae) was used as “bait” to isolate pathogenic fungi from soil. Ninety soil samples were collected from woodlands and pastures in the vicinities of Baton Rouge, New Orleans, and Lake Charles, LA, from which six Metarhizium anisopliae (Metsch.) Sorokin and nine Beauveria bassiana (Balsamo) Vuillemin isolates were obtained. Numbers of fungal isolates from the three sampling locations did not differ, but more isolates were found in woodlands than in pastures. Median lethal doses (LD50s) of these fungal species to C. formosanus were interspersed, indicating that fungal isolates rather than species had the greatest effect on virulence. Among nine Louisiana and two USDA isolates of B. bassiana, LD50s ranged from 4.95 × 103 to 4.96 × 105 conidia/termite, a difference of 100×. LD50s of six Louisiana and four USDA isolates of M. anisopliae ranged from 7.89 × 103 to 1.22 × 105 conidia/termite. Survival time also was used to compare virulence; M. anisopliae infections caused significantly shorter host survival times than B. bassiana. In vitro growth characteristics were significantly correlated with virulence against termites, suggesting that the characteristics of a fungus growing on agar might contribute to estimating the fungal virulence in vivo.

scholarly journals The Role of IL-33 in Host Response toCandida albicans

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
C. Rodríguez-Cerdeira ◽  
A. Lopez-Bárcenas ◽  
B. Sánchez-Blanco ◽  
R. Arenas
Keyword(s):  
Defense Mechanisms ◽  
Fungal Pathogens ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Case Reports ◽  
Pathogenic Fungi ◽  
Cell Types ◽  
Immune Defense ◽  
Beneficial Role

Background. Interleukin (IL) 33 is a recently identified pleiotropic cytokine that influences the activity of multiple cell types and orchestrates complex innate and adaptive immune responses.Methods. We performed an extensive review of the literature published between 2005 and 2013 on IL-33 and related cytokines, their functions, and their regulation of the immune system followingCandida albicanscolonization. Our literature review included cross-references from retrieved articles and specific data from our own studies.Results. IL-33 (IL-1F11) is a recently identified member of the IL-1 family of cytokines. Accumulating evidence suggests a pivotal role of the IL-33/ST2 axis in host immune defense against fungal pathogens, includingC. albicans. IL-33 induces a Th2-type inflammatory response and activates both innate and adaptive immunity. Studies in animal models have shown that Th2 inflammatory responses have a beneficial role in immunity against gastrointestinal and systemic infections byCandidaspp.Conclusions. This review summarizes the most important clinical studies and case reports describing the beneficial role of IL-33 in immunity and host defense mechanisms against pathogenic fungi. The finding that the IL-33/ST2 axis is involved in therapeutic target has implications for the prevention and treatment of inflammatory diseases, including acute or chronic candidiasis.

scholarly journals Identification and Phenotypic Characterization of Hsp90 Phosphorylation Sites That Modulate Virulence Traits in the Major Human Fungal Pathogen Candida albicans

2021 ◽  
Vol 11 ◽  
Author(s):  
Leenah Alaalm ◽  
Julia L. Crunden ◽  
Mark Butcher ◽  
Ulrike Obst ◽  
Ryann Whealy ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Environmental Stress ◽  
Stress Responses ◽  
Fungal Pathogens ◽  
Phosphorylation Site ◽  
Pathogenic Fungi ◽  
Phenotypic Characterization ◽  
Fungal Virulence ◽  
Post Translational Modifications ◽  
Virulence Traits

The highly conserved, ubiquitous molecular chaperone Hsp90 is a key regulator of cellular proteostasis and environmental stress responses. In human pathogenic fungi, which kill more than 1.6 million patients each year worldwide, Hsp90 governs cellular morphogenesis, drug resistance, and virulence. Yet, our understanding of the regulatory mechanisms governing fungal Hsp90 function remains sparse. Post-translational modifications are powerful components of nature’s toolbox to regulate protein abundance and function. Phosphorylation in particular is critical in many cellular signaling pathways and errant phosphorylation can have dire consequences for the cell. In the case of Hsp90, phosphorylation affects its stability and governs its interactions with co-chaperones and clients. Thereby modulating the cell’s ability to cope with environmental stress. Candida albicans, one of the leading human fungal pathogens, causes ~750,000 life-threatening invasive infections worldwide with unacceptably high mortality rates. Yet, it remains unknown if and how Hsp90 phosphorylation affects C. albicans virulence traits. Here, we show that phosphorylation of Hsp90 is critical for expression of virulence traits. We combined proteomics, molecular evolution analyses and structural modeling with molecular biology to characterize the role of Hsp90 phosphorylation in this non-model pathogen. We demonstrated that phosphorylation negatively affects key virulence traits, such as the thermal stress response, morphogenesis, and drug susceptibility. Our results provide the first record of a specific Hsp90 phosphorylation site acting as modulator of fungal virulence. Post-translational modifications of Hsp90 could prove valuable in future exploitations as antifungal drug targets.

scholarly journals Remote homology clustering identifies lowly conserved families of effector proteins in plant-pathogenic fungi

2021 ◽  
Vol 7 (9) ◽  
Author(s):  
Darcy A. B. Jones ◽  
Paula M. Moolhuijzen ◽  
James K. Hane
Keyword(s):  
Fungal Pathogens ◽  
Pathogenic Fungi ◽  
Comparison Method ◽  
Fungal Species ◽  
Effector Proteins ◽  
Plant Diseases ◽  
Plant Host ◽  
Homology Inference ◽  
Developing Area ◽  
Inference Methods

Plant diseases caused by fungal pathogens are typically initiated by molecular interactions between ‘effector’ molecules released by a pathogen and receptor molecules on or within the plant host cell. In many cases these effector-receptor interactions directly determine host resistance or susceptibility. The search for fungal effector proteins is a developing area in fungal-plant pathology, with more than 165 distinct confirmed fungal effector proteins in the public domain. For a small number of these, novel effectors can be rapidly discovered across multiple fungal species through the identification of known effector homologues. However, many have no detectable homology by standard sequence-based search methods. This study employs a novel comparison method (RemEff) that is capable of identifying protein families with greater sensitivity than traditional homology-inference methods, leveraging a growing pool of confirmed fungal effector data to enable the prediction of novel fungal effector candidates by protein family association. Resources relating to the RemEff method and data used in this study are available from https://figshare.com/projects/Effector_protein_remote_homology/87965.

scholarly journals Comparative Genomics and the Evolution of Pathogenicity in Human Pathogenic Fungi

2010 ◽  
Vol 10 (1) ◽  
pp. 34-42 ◽  
Author(s):  
Gary P. Moran ◽  
David C. Coleman ◽  
Derek J. Sullivan
Keyword(s):  
Fungal Pathogens ◽  
Direct Interaction ◽  
Pathogenic Fungi ◽  
Gene Families ◽  
Fungal Pathogenesis ◽  
Individual Species ◽  
Fungal Virulence ◽  
Content Type ◽  
Sequencing Technologies ◽  
Genes Encoding

ABSTRACTBecause most fungi have evolved to be free-living in the environment and because the infections they cause are usually opportunistic in nature, it is often difficult to identify specific traits that contribute to fungal pathogenesis. In recent years, there has been a surge in the number of sequenced genomes of human fungal pathogens, and comparison of these sequences has proved to be an excellent resource for exploring commonalities and differences in how these species interact with their hosts. In order to survive in the human body, fungi must be able to adapt to new nutrient sources and environmental stresses. Therefore, genes involved in carbohydrate and amino acid metabolism and transport and genes encoding secondary metabolites tend to be overrepresented in pathogenic species (e.g.,Aspergillus fumigatus). However, it is clear that human commensal yeast species such asCandida albicanshave also evolved a range of specific factors that facilitate direct interaction with host tissues. The evolution of virulence across the human pathogenic fungi has occurred largely through very similar mechanisms. One of the most important mechanisms is gene duplication and the expansion of gene families, particularly in subtelomeric regions. Unlike the case for prokaryotic pathogens, horizontal transfer of genes between species and other genera does not seem to have played a significant role in the evolution of fungal virulence. New sequencing technologies promise the prospect of even greater numbers of genome sequences, facilitating the sequencing of multiple genomes and transcriptomes within individual species, and will undoubtedly contribute to a deeper insight into fungal pathogenesis.

scholarly journals A circadian oscillator in the fungus Botrytis cinerea regulates virulence when infecting Arabidopsis thaliana

2015 ◽  
Vol 112 (28) ◽  
pp. 8744-8749 ◽  
Author(s):  
Montserrat A. Hevia ◽  
Paulo Canessa ◽  
Hanna Müller-Esparza ◽  
Luis F. Larrondo
Keyword(s):  
Arabidopsis Thaliana ◽  
Botrytis Cinerea ◽  
Plant Pathogen ◽  
Defense Mechanisms ◽  
Pathogenic Fungi ◽  
Circadian System ◽  
Main Role ◽  
Fungal Virulence ◽  
Virulence Potential ◽  
Plant Pathogen Interactions

The circadian clock of the plant model Arabidopsis thaliana modulates defense mechanisms impacting plant–pathogen interactions. Nevertheless, the effect of clock regulation on pathogenic traits has not been explored in detail. Moreover, molecular description of clocks in pathogenic fungi—or fungi in general other than the model ascomycete Neurospora crassa—has been neglected, leaving this type of question largely unaddressed. We sought to characterize, therefore, the circadian system of the plant pathogen Botrytis cinerea to assess if such oscillatory machinery can modulate its virulence potential. Herein, we show the existence of a functional clock in B. cinerea, which shares similar components and circuitry with the Neurospora circadian system, although we found that its core negative clock element FREQUENCY (BcFRQ1) serves additional roles, suggesting extracircadian functions for this protein. We observe that the lesions produced by this necrotrophic fungus on Arabidopsis leaves are smaller when the interaction between these two organisms occurs at dawn. Remarkably, this effect does not depend solely on the plant clock, but instead largely relies on the pathogen circadian system. Genetic disruption of the B. cinerea oscillator by mutation, overexpression of BcFRQ1, or by suppression of its rhythmicity by constant light, abrogates circadian regulation of fungal virulence. By conducting experiments with out-of-phase light:dark cycles, we confirm that indeed, it is the fungal clock that plays the main role in defining the outcome of the Arabidopsis–Botrytis interaction, providing to our knowledge the first evidence of a microbial clock modulating pathogenic traits at specific times of the day.

scholarly journals Interplay between Candida albicans and the Antimicrobial Peptide Armory

2014 ◽  
Vol 13 (8) ◽  
pp. 950-957 ◽  
Author(s):  
Marc Swidergall ◽  
Joachim F. Ernst
Keyword(s):  
Candida Albicans ◽  
Defense Mechanisms ◽  
Fungal Pathogens ◽  
Pathogenic Fungi ◽  
Resistance Mechanisms ◽  
Immune Defense ◽  
Basal Resistance ◽  
Content Type ◽  
Normal Human ◽  
Molecular Patterns

ABSTRACTAntimicrobial peptides (AMPs) are key elements of innate immunity, which can directly kill multiple bacterial, viral, and fungal pathogens. The medically important fungusCandida albicanscolonizes different host niches as part of the normal human microbiota. Proliferation ofC. albicansis regulated through a complex balance of host immune defense mechanisms and fungal responses. Expression of AMPs against pathogenic fungi is differentially regulated and initiated by interactions of a variety of fungal pathogen-associated molecular patterns (PAMPs) with pattern recognition receptors (PRRs) on human cells. Inflammatory signaling and other environmental stimuli are also essential to control fungal proliferation and to prevent parasitism. To persist in the host,C. albicanshas developed a three-phase AMP evasion strategy, including secretion of peptide effectors, AMP efflux pumps, and regulation of signaling pathways. These mechanisms preventC. albicansfrom the antifungal activity of the major AMP classes, including cathelicidins, histatins, and defensins leading to a basal resistance. This minireview summarizes human AMP attack andC. albicansresistance mechanisms and current developments in the use of AMPs as antifungal agents.

scholarly journals Fungal pathogens of the genus Fusarium in winter wheat Triticum aestivum L. protected with fungicides in north-eastern Poland

2013 ◽  
Vol 66 (2) ◽  
pp. 95-106 ◽  
Author(s):  
Agnieszka Pszczółkowska ◽  
Adam Okorski ◽  
Jacek Olszewski ◽  
Joanna Jarmołkowicz
Keyword(s):  
Winter Wheat ◽  
Fungal Pathogens ◽  
Crop Protection ◽  
Pathogenic Fungi ◽  
Triticum Aestivum L ◽  
Fungal Species ◽  
Diagnostic Methods ◽  
Growth Stages ◽  
Monthly Precipitation ◽  
Wheat Grain

Various diagnostic methods were used to evaluate the effect of fungicide protection on the prevalence of pathogenic fungi in wheat grain. Winter wheat cv. Nutka and Zyta was grown during a field experiment established in the Production and Experimental Station in Bałcyny in 2006–2007. The experimental factor was chemical crop protection: epoxiconazole, kresoxim-methyl and fenpropimorph applied at growth stages BBCH 33–35 as well as dimoxystrobin and epoxiconazole applied at BBCH 51–53. In this experiment, microscopic observations and conventional PCR assays were used as complementary methods. The quantification of <em>Fusarium</em> <em>poae</em> DNA by qPCR demonstrated the effectiveness of chemical protection against the analyzed fungal species. Lower monthly precipitation levels and higher daily temperatures intensified grain infections, in particular those caused by <em>F</em>. <em>poae</em>. A significant correlation was determined between the number of <em>F</em>. <em>poae</em> cultures isolated from winter wheat grain and the quantity of pathogenic DNA in grain identified by qPCR. Grain infections caused by <em>F</em>.<em> poae</em> lowered yield and thousand seed weight.

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