Editorial

4 pages, 184 KiB

Open AccessEditorial

by Jennifer Geddes-McAlister

J. Fungi 2022, 8(5), 478; https://doi.org/10.3390/jof8050478 - 04 May 2022

Viewed by 1436

The beauty within biological systems can be uncovered using a variety of advanced technological platforms for in-depth profiling. Improvements in genome, transcriptome, proteome, and metabolome investigations, as well as data integration, are moving our understanding of diverse biological systems forward at a rapid [...] Read more.

The beauty within biological systems can be uncovered using a variety of advanced technological platforms for in-depth profiling. Improvements in genome, transcriptome, proteome, and metabolome investigations, as well as data integration, are moving our understanding of diverse biological systems forward at a rapid rate. Combined with publicly available and customizable bioinformatics tools, we comprehensively profile biological changes under a plethora of circumstances. For fungal pathogens innovation is driven by our ability to explore mechanisms of antifungal resistance, reveal new relationships and interactions between a host and pathogen, improve our characterization of virulence determinants, and discover new antifungal targets. In this Special Issue dedicated to “Systems biology in fungal research”, we explore each of these factors and more, highlighting the multitude of avenues and strategies available to study fungal pathogens and how they impact our environment. Full article

(This article belongs to the Special Issue Systems Biology in Fungal Research)

Research

Jump to: Editorial, Review

13 pages, 3127 KiB

Open AccessArticle

Heterologous Synthesis of Monacolin J by Reconstructing Its Biosynthetic Gene Cluster in Aspergillus niger

by Xu Zeng, Junwei Zheng, Feifei Lu, Li Pan and Bin Wang

J. Fungi 2022, 8(4), 407; https://doi.org/10.3390/jof8040407 - 16 Apr 2022

Cited by 3 | Viewed by 2522

Abstract

Monacolin J (MJ), a key precursor of Lovastatin, could synthesize important statin drug simvastatin by hydrolyzing lovastatin and adding different side chains. In this study, to reduce the cumbersome hydrolysis of lovastatin to produce MJ in the native strain Aspergillus terreus, the [...] Read more.

Monacolin J (MJ), a key precursor of Lovastatin, could synthesize important statin drug simvastatin by hydrolyzing lovastatin and adding different side chains. In this study, to reduce the cumbersome hydrolysis of lovastatin to produce MJ in the native strain Aspergillus terreus, the MJ biosynthetic pathway genes (lovB, lovC, lovG, and lovA) were heterologously integrated into the genome of Aspergillus. niger CBS513.88 with strong promoters and suitable integration sites, via yeast 2μ homologous recombination to construct expression cassettes of long-length genes and CRISPR/Cas9 homology-directed recombination (CRISPR-HDR) to integrate MJ genes in the genome of A. niger. RT-PCR results proved that pathway synthesis-related genes could be heterologously expressed in A. niger. Finally, we constructed an engineered strain that could produce monacolin J, detected by LC-HR-ESIMS (MJ, 339.22 [M-H]⁺). The yield of MJ reached 92.90 mg/L after 7-day cultivation. By optimizing the cultivation conditions and adding precursor, the final titer of MJ was 142.61 mg/L on the fourth day of fed-batch cultivation, which was increased by 53.5% compared to the original growth conditions. Due to the wide application of A. niger in industrial fermentation for food and medicine, the following work will be dedicated to optimizing the metabolic network to improve the MJ production in the engineered strain. Full article

(This article belongs to the Special Issue Systems Biology in Fungal Research)

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18 pages, 4243 KiB

Open AccessArticle

Effects of Trichoderma asperellum 6S-2 on Apple Tree Growth and Replanted Soil Microbial Environment

by Haiyan Wang, Rong Zhang, Yunfei Mao, Weitao Jiang, Xuesen Chen, Xiang Shen, Chengmiao Yin and Zhiquan Mao

J. Fungi 2022, 8(1), 63; https://doi.org/10.3390/jof8010063 - 07 Jan 2022

Cited by 9 | Viewed by 3070

Abstract

Trichoderma asperellum strain 6S-2 with biocontrol effects and potential growth-promoting properties was made into a fungal fertilizer for the prevention of apple replant disease (ARD). 6S-2 fertilizer not only promoted the growth of Malus hupehensis Rehd seedlings in greenhouse and pot experiments, but [...] Read more.

Trichoderma asperellum strain 6S-2 with biocontrol effects and potential growth-promoting properties was made into a fungal fertilizer for the prevention of apple replant disease (ARD). 6S-2 fertilizer not only promoted the growth of Malus hupehensis Rehd seedlings in greenhouse and pot experiments, but also increased the branch elongation growth of young apple trees. The soil microbial community structure changed significantly after the application of 6S-2 fertilizer: the relative abundance of Trichoderma increased significantly, the relative abundance of Fusarium (especially the gene copy numbers of four Fusarium species) and Cryptococcus decreased, and the relative abundance of Bacillus and Streptomyces increased. The bacteria/fungi and soil enzyme activities increased significantly after the application of 6S-2 fertilizer. The relative contents of alkenes, ethyl ethers, and citrullines increased in root exudates of M. hupehensis Rehd treated with 6S-2 fertilizer and were positively correlated with the abundance of Trichoderma. The relative contents of aldehydes, nitriles, and naphthalenes decreased, and they were positively correlated with the relative abundance of Fusarium. In addition, levels of ammonium nitrogen (NH₄-N), nitrate nitrogen (NO₃-N), available phosphorus (AP), available potassium (AK), organic matter (SOM), and pH in rhizosphere soil were also significantly related to changes in the microbial community structure. In summary, the application of 6S-2 fertilizer was effective in alleviating some aspects of ARD by promoting plant growth and optimizing the soil microbial community structure. Full article

(This article belongs to the Special Issue Systems Biology in Fungal Research)

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27 pages, 5589 KiB

Open AccessArticle

The Endophytic Strain Trichoderma asperellum 6S-2: An Efficient Biocontrol Agent against Apple Replant Disease in China and a Potential Plant-Growth-Promoting Fungus

by Haiyan Wang, Rong Zhang, Yanan Duan, Weitao Jiang, Xuesen Chen, Xiang Shen, Chengmiao Yin and Zhiquan Mao

J. Fungi 2021, 7(12), 1050; https://doi.org/10.3390/jof7121050 - 08 Dec 2021

Cited by 22 | Viewed by 3911

Abstract

A study was conducted for endophytic antagonistic fungi obtained from the roots of healthy apple trees growing in nine replanted orchards in Shandong Province, China. The fungi were assessed for their ability to inhibit Fusarium proliferatum f. sp. malus domestica MR5, a fungal [...] Read more.

A study was conducted for endophytic antagonistic fungi obtained from the roots of healthy apple trees growing in nine replanted orchards in Shandong Province, China. The fungi were assessed for their ability to inhibit Fusarium proliferatum f. sp. malus domestica MR5, a fungal strain associated with apple replant disease (ARD). An effective endophyte, designated as strain 6S-2, was isolated and identified as Trichoderma asperellum. Strain 6S-2 demonstrated protease, amylase, cellulase, and laccase activities, which are important for the parasitic and antagonistic functions of pathogenic fungi. The inhibition rate of 6S-2 against Fusarium proliferatum f. sp. malus domestica MR5 was 52.41%. Strain 6S-2 also secreted iron carriers, auxin, ammonia and was able to solubilize phosphorus. Its fermentation extract and volatile substances inhibited the growth of MR5, causing its hyphae to twist, shrink, swell, and rupture. The antifungal activity of the 6S-2 fermentation extract increased with increasing concentrations. It promoted the production and elongation of Arabidopsis thaliana lateral roots, and the strongest effects were seen at a concentration of 50 mg/mL. A GC-MS analysis of the 6S-2 fermentation extract and volatile substances showed that they comprised mainly alkanes, alcohols, and furanones, as well as the specific volatile substance 6-PP. The application of 6S-2 spore suspension to replanted apple orchard soils reduced plant oxidative damage and promoted plant growth in a pot experiment. Therefore, the endophytic strain T. asperellum 6S-2 has the potential to serve as an effective biocontrol fungus for the prevention of ARD in China, and appears to promote plant growth. Full article

(This article belongs to the Special Issue Systems Biology in Fungal Research)

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17 pages, 2492 KiB

Open AccessEditor’s ChoiceArticle

Bile Acid Regulates the Colonization and Dissemination of Candida albicans from the Gastrointestinal Tract by Controlling Host Defense System and Microbiota

by Shankar Thangamani, Ross Monasky, Jung Keun Lee, Vijay Antharam, Harm HogenEsch, Tony R. Hazbun, Yan Jin, Haiwei Gu and Grace L. Guo

J. Fungi 2021, 7(12), 1030; https://doi.org/10.3390/jof7121030 - 30 Nov 2021

Cited by 7 | Viewed by 3382

Abstract

Candida albicans (CA), a commensal and opportunistic eukaryotic organism, frequently inhabits the gastrointestinal (GI) tract and causes life-threatening infections. Antibiotic-induced gut dysbiosis is a major risk factor for increased CA colonization and dissemination from the GI tract. We identified a significant increase of [...] Read more.

Candida albicans (CA), a commensal and opportunistic eukaryotic organism, frequently inhabits the gastrointestinal (GI) tract and causes life-threatening infections. Antibiotic-induced gut dysbiosis is a major risk factor for increased CA colonization and dissemination from the GI tract. We identified a significant increase of taurocholic acid (TCA), a major bile acid in antibiotic-treated mice susceptible to CA infection. In vivo findings indicate that administration of TCA through drinking water is sufficient to induce colonization and dissemination of CA in wild-type and immunosuppressed mice. Treatment with TCA significantly reduced mRNA expression of immune genes ang4 and Cxcr3 in the colon. In addition, TCA significantly decreased the relative abundance of three culturable species of commensal bacteria, Turicibacter sanguinis, Lactobacillus johnsonii, and Clostridium celatum, in both cecal contents and mucosal scrapings from the colon. Taken together, our results indicate that TCA promotes fungal colonization and dissemination of CA from the GI tract by controlling the host defense system and intestinal microbiota that play a critical role in regulating CA in the intestine. Full article

(This article belongs to the Special Issue Systems Biology in Fungal Research)

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15 pages, 947 KiB

Open AccessArticle

Probiotic Properties and Potentiality of Lactiplantibacillus plantarum Strains for the Biological Control of Chalkbrood Disease

by Massimo Iorizzo, Bruno Testa, Sonia Ganassi, Silvia Jane Lombardi, Mario Ianiro, Francesco Letizia, Mariantonietta Succi, Patrizio Tremonte, Franca Vergalito, Autilia Cozzolino, Elena Sorrentino, Sonia Petrarca, Antonio De Cristofaro and Raffaele Coppola

J. Fungi 2021, 7(5), 379; https://doi.org/10.3390/jof7050379 - 12 May 2021

Cited by 13 | Viewed by 3064

Abstract

Ascosphaera apis is an entomopathogenic fungus that affects honeybees. In stressful conditions, this fungus (due not only to its presence, but also to the combination of other biotic and abiotic stressors) can cause chalkbrood disease. In recent years, there has been increasing attention [...] Read more.

Ascosphaera apis is an entomopathogenic fungus that affects honeybees. In stressful conditions, this fungus (due not only to its presence, but also to the combination of other biotic and abiotic stressors) can cause chalkbrood disease. In recent years, there has been increasing attention paid towards the use of lactic acid bacteria (LAB) in the honeybees’ diets to improve their health, productivity and ability to resist infections by pathogenic microorganisms. The screening of 22 strains of Lactiplantibacillus plantarum, isolated from the gastrointestinal tracts of honeybees and beebread, led to the selection of five strains possessing high antagonistic activity against A. apis. This study focused on the antifungal activity of these five strains against A. apis DSM 3116 and DSM 3117 using different matrices: cell lysate, broth culture, cell-free supernatant and cell pellet. In addition, some functional properties and the antioxidant activity of the five L. plantarum strains were evaluated. All five strains exhibited high antagonistic activity against A. apis, good surface cellular properties (extracellular polysaccharide (EPS) production and biofilm formation) and antioxidant activity. Although preliminary, these results are encouraging, and in future investigations, the effectiveness of these bacteria as probiotics in honeybee nutrition will be tested in vivo in the context of an eco-friendly strategy for the biological control of chalkbrood disease. Full article

(This article belongs to the Special Issue Systems Biology in Fungal Research)

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10 pages, 2125 KiB

Open AccessArticle

Identification of a Novel Biosynthetic Gene Cluster in Aspergillus niger Using Comparative Genomics

by Gregory Evdokias, Cameron Semper, Montserrat Mora-Ochomogo, Marcos Di Falco, Thi Truc Minh Nguyen, Alexei Savchenko, Adrian Tsang and Isabelle Benoit-Gelber

J. Fungi 2021, 7(5), 374; https://doi.org/10.3390/jof7050374 - 11 May 2021

Cited by 8 | Viewed by 3330

Abstract

Previously, DNA microarrays analysis showed that, in co-culture with Bacillus subtilis, a biosynthetic gene cluster anchored with a nonribosomal peptides synthetase of Aspergillus niger is downregulated. Based on phylogenetic and synteny analyses, we show here that this gene cluster, NRRL3_00036-NRRL3_00042, comprises [...] Read more.

Previously, DNA microarrays analysis showed that, in co-culture with Bacillus subtilis, a biosynthetic gene cluster anchored with a nonribosomal peptides synthetase of Aspergillus niger is downregulated. Based on phylogenetic and synteny analyses, we show here that this gene cluster, NRRL3_00036-NRRL3_00042, comprises genes predicted to encode a nonribosomal peptides synthetase, a FAD-binding domain-containing protein, an uncharacterized protein, a transporter, a cytochrome P450 protein, a NAD(P)-binding domain-containing protein and a transcription factor. We overexpressed the in-cluster transcription factor gene NRRL3_00042. The overexpression strain, NRRL3_00042^OE, displays reduced growth rate and production of a yellow pigment, which by mass spectrometric analysis corresponds to two compounds with masses of 409.1384 and 425.1331. We deleted the gene encoding the NRRL3_00036 nonribosomal peptides synthetase in the NRRL3_00042^OE strain. The resulting strain reverted to the wild-type phenotype. These results suggest that the biosynthetic gene cluster anchored by the NRRL3_00036 nonribosomal peptides synthetase gene is regulated by the in-cluster transcriptional regulator gene NRRL3_00042, and that it is involved in the production of two previously uncharacterized compounds. Full article

(This article belongs to the Special Issue Systems Biology in Fungal Research)

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29 pages, 4434 KiB

Open AccessArticle

Comparison of Plant Metabolites in Root Exudates of Lolium perenne Infected with Different Strains of the Fungal Endophyte Epichloë festucae var. lolii

by Aurora Patchett and Jonathan A. Newman

J. Fungi 2021, 7(2), 148; https://doi.org/10.3390/jof7020148 - 18 Feb 2021

Cited by 20 | Viewed by 2911

Abstract

Lolium perenne infected with the fungal endophyte Epichloë festucae var. lolii have specific, endophyte strain-dependent, chemical phenotypes in their above-ground tissues. Differences in these chemical phenotypes have been largely associated with classes of fungal-derived alkaloids which protect the plant against many insect pests. [...] Read more.

Lolium perenne infected with the fungal endophyte Epichloë festucae var. lolii have specific, endophyte strain-dependent, chemical phenotypes in their above-ground tissues. Differences in these chemical phenotypes have been largely associated with classes of fungal-derived alkaloids which protect the plant against many insect pests. However, the use of new methodologies, such as various omic techniques, has demonstrated that many other chemical changes occur in both primary and secondary metabolites. Few studies have investigated changes in plant metabolites exiting the plant in the form of root exudates. As root exudates play an essential role in the acquisition of nutrients, microbial associations, and defense in the below-ground environment, it is of interest to understand how plant root exudate chemistry is influenced by the presence of strains of a fungal endophyte. In this study, we tested the influence of four strains of E. festucae var. lolii (E+ (also known as Lp19), AR1, AR37, NEA2), and uninfected controls (E−), on L. perenne growth and the composition of root exudate metabolites. Root exudates present in the hydroponic water were assessed by untargeted metabolomics using Accurate-Mass Quadrupole Time-of-Flight (Q–TOF) liquid chromatography–mass spectrometry (LC–MS). The NEA2 endophyte strain resulted in the greatest plant biomass and the lowest endophyte concentration. We found 84 metabolites that were differentially expressed in at least one of the endophyte treatments compared to E− plants. Two compounds were strongly associated with one endophyte treatment, one in AR37 (m/z 135.0546 RT 1.17), and one in E+ (m/z 517.1987 RT 9.26). These results provide evidence for important changes in L. perenne physiology in the presence of different fungal endophyte strains. Further research should aim to connect changes in root exudate chemical composition with soil ecosystem processes. Full article

(This article belongs to the Special Issue Systems Biology in Fungal Research)

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39 pages, 4773 KiB

Open AccessArticle

Examining the Impacts of CO₂ Concentration and Genetic Compatibility on Perennial Ryegrass—Epichloë festucae var lolii Interactions

by Jennifer Geddes-McAlister, Arjun Sukumaran, Aurora Patchett, Heather A. Hager, Jenna C. M. Dale, Jennifer L. Roloson, Nicholas Prudhomme, Kim Bolton, Benjamin Muselius, Jacqueline Powers and Jonathan A. Newman

J. Fungi 2020, 6(4), 360; https://doi.org/10.3390/jof6040360 - 11 Dec 2020

Cited by 8 | Viewed by 3224

Abstract

Perennial ryegrass (Lolium perenne) is the most cultivated cool-season grass worldwide with crucial roles in carbon fixation, turfgrass applications, and fodder for livestock. Lolium perenne forms a mutualism with the strictly vertically transmitted fungal endophyte, Epichloë festucae var lolii. The [...] Read more.

Perennial ryegrass (Lolium perenne) is the most cultivated cool-season grass worldwide with crucial roles in carbon fixation, turfgrass applications, and fodder for livestock. Lolium perenne forms a mutualism with the strictly vertically transmitted fungal endophyte, Epichloë festucae var lolii. The fungus produces alkaloids that protect the grass from herbivory, as well as conferring protection from drought and nutrient stress. The rising concentration of atmospheric CO₂, a proximate cause of climatic change, is known to have many direct and indirect effects on plant growth. There is keen interest in how the nature of this plant–fungal interaction will change with climate change. Lolium perenne is an obligately outcrossing species, meaning that the genetic profile of the host is constantly being reshuffled. Meanwhile, the fungus is asexual implying both a relatively constant genetic profile and the potential for incompatible grass–fungus pairings. In this study, we used a single cultivar, “Alto”, of L. perenne. Each plant was infected with one of four strains of the endophyte: AR1, AR37, NEA2, and Lp19 (the “common strain”). We outcrossed the Alto mothers with pollen from a number of individuals from different ryegrass cultivars to create more genetic diversity in the hosts. We collected seed such that we had replicate maternal half-sib families. Seed from each family was randomly allocated into the two levels of the CO₂ treatment, 400 and 800 ppm. Elevated CO₂ resulted in an c. 18% increase in plant biomass. AR37 produced higher fungal concentrations than other strains; NEA2 produced the lowest fungal concentrations. We did not find evidence of genetic incompatibility between the host plants and the fungal strains. We conducted untargeted metabolomics and quantitative proteomics to investigate the grass-fungus interactions between and within family and treatment groups. We identified a number of changes in both the proteome and metabalome. Taken together, our data set provides new understanding into the intricacy of the interaction between endophyte and host from multiple molecular levels and suggests opportunity to promote plant robustness and survivability in rising CO₂ environmental conditions through application of bioprotective epichloid strains. Full article

(This article belongs to the Special Issue Systems Biology in Fungal Research)

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19 pages, 1138 KiB

Open AccessArticle

Genome-Scale Metabolic Model of the Human Pathogen Candida albicans: A Promising Platform for Drug Target Prediction

by Romeu Viana, Oscar Dias, Davide Lagoa, Mónica Galocha, Isabel Rocha and Miguel Cacho Teixeira

J. Fungi 2020, 6(3), 171; https://doi.org/10.3390/jof6030171 - 11 Sep 2020

Cited by 13 | Viewed by 4901

Abstract

Candida albicans is one of the most impactful fungal pathogens and the most common cause of invasive candidiasis, which is associated with very high mortality rates. With the rise in the frequency of multidrug-resistant clinical isolates, the identification of new drug targets and [...] Read more.

Candida albicans is one of the most impactful fungal pathogens and the most common cause of invasive candidiasis, which is associated with very high mortality rates. With the rise in the frequency of multidrug-resistant clinical isolates, the identification of new drug targets and new drugs is crucial in overcoming the increase in therapeutic failure. In this study, the first validated genome-scale metabolic model for Candida albicans, iRV781, is presented. The model consists of 1221 reactions, 926 metabolites, 781 genes, and four compartments. This model was reconstructed using the open-source software tool merlin 4.0.2. It is provided in the well-established systems biology markup language (SBML) format, thus, being usable in most metabolic engineering platforms, such as OptFlux or COBRA. The model was validated, proving accurate when predicting the capability of utilizing different carbon and nitrogen sources when compared to experimental data. Finally, this genome-scale metabolic reconstruction was tested as a platform for the identification of drug targets, through the comparison between known drug targets and the prediction of gene essentiality in conditions mimicking the human host. Altogether, this model provides a promising platform for global elucidation of the metabolic potential of C. albicans, possibly guiding the identification of new drug targets to tackle human candidiasis. Full article

(This article belongs to the Special Issue Systems Biology in Fungal Research)

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Review

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13 pages, 654 KiB

Open AccessReview

From Naturally-Sourced Protease Inhibitors to New Treatments for Fungal Infections

by Davier Gutierrez-Gongora and Jennifer Geddes-McAlister

J. Fungi 2021, 7(12), 1016; https://doi.org/10.3390/jof7121016 - 27 Nov 2021

Cited by 13 | Viewed by 5800

Abstract

Proteases are involved in a broad range of physiological processes, including host invasion by fungal pathogens, and enzymatic inhibition is a key molecular mechanism controlling proteolytic activity. Importantly, inhibitors from natural or synthetic sources have demonstrated applications in biochemistry, biotechnology, and biomedicine. However, [...] Read more.

Proteases are involved in a broad range of physiological processes, including host invasion by fungal pathogens, and enzymatic inhibition is a key molecular mechanism controlling proteolytic activity. Importantly, inhibitors from natural or synthetic sources have demonstrated applications in biochemistry, biotechnology, and biomedicine. However, the need to discover new reservoirs of these inhibitory molecules with improved efficacy and target range has been underscored by recent protease characterization related to infection and antimicrobial resistance. In this regard, naturally-sourced inhibitors show promise for application in diverse biological systems due to high stability at physiological conditions and low cytotoxicity. Moreover, natural sources (e.g., plants, invertebrates, and microbes) provide a large reservoir of undiscovered and/or uncharacterized bioactive molecules involved in host defense against predators and pathogens. In this Review, we highlight discoveries of protease inhibitors from environmental sources, propose new opportunities for assessment of antifungal activity, and discuss novel applications to combat biomedically-relevant fungal diseases with in vivo and clinical purpose. Full article

(This article belongs to the Special Issue Systems Biology in Fungal Research)

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15 pages, 1430 KiB

Open AccessReview

Chaperone Networks in Fungal Pathogens of Humans

by Linda C. Horianopoulos and James W. Kronstad

J. Fungi 2021, 7(3), 209; https://doi.org/10.3390/jof7030209 - 12 Mar 2021

Cited by 10 | Viewed by 3424

Abstract

The heat shock proteins (HSPs) function as chaperones to facilitate proper folding and modification of proteins and are of particular importance when organisms are subjected to unfavourable conditions. The human fungal pathogens are subjected to such conditions within the context of infection as [...] Read more.

The heat shock proteins (HSPs) function as chaperones to facilitate proper folding and modification of proteins and are of particular importance when organisms are subjected to unfavourable conditions. The human fungal pathogens are subjected to such conditions within the context of infection as they are exposed to human body temperature as well as the host immune response. Herein, the roles of the major classes of HSPs are briefly reviewed and their known contributions in human fungal pathogens are described with a focus on Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus. The Hsp90s and Hsp70s in human fungal pathogens broadly contribute to thermotolerance, morphological changes required for virulence, and tolerance to antifungal drugs. There are also examples of J domain co-chaperones and small HSPs influencing the elaboration of virulence factors in human fungal pathogens. However, there are diverse members in these groups of chaperones and there is still much to be uncovered about their contributions to pathogenesis. These HSPs do not act in isolation, but rather they form a network with one another. Interactions between chaperones define their specific roles and enhance their protein folding capabilities. Recent efforts to characterize these HSP networks in human fungal pathogens have revealed that there are unique interactions relevant to these pathogens, particularly under stress conditions. The chaperone networks in the fungal pathogens are also emerging as key coordinators of pathogenesis and antifungal drug tolerance, suggesting that their disruption is a promising strategy for the development of antifungal therapy. Full article

(This article belongs to the Special Issue Systems Biology in Fungal Research)

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15 pages, 2044 KiB

Open AccessReview

Post-Translational Modifications Drive Success and Failure of Fungal–Host Interactions

by Charmaine Retanal, Brianna Ball and Jennifer Geddes-McAlister

J. Fungi 2021, 7(2), 124; https://doi.org/10.3390/jof7020124 - 09 Feb 2021

Cited by 19 | Viewed by 4166

Abstract

Post-translational modifications (PTMs) change the structure and function of proteins and regulate a diverse array of biological processes. Fungal pathogens rely on PTMs to modulate protein production and activity during infection, manipulate the host response, and ultimately, promote fungal survival. Given the high [...] Read more.

Post-translational modifications (PTMs) change the structure and function of proteins and regulate a diverse array of biological processes. Fungal pathogens rely on PTMs to modulate protein production and activity during infection, manipulate the host response, and ultimately, promote fungal survival. Given the high mortality rates of fungal infections on a global scale, along with the emergence of antifungal-resistant species, identifying new treatment options is critical. In this review, we focus on the role of PTMs (e.g., phosphorylation, acetylation, ubiquitination, glycosylation, and methylation) among the highly prevalent and medically relevant fungal pathogens, Candida spp., Aspergillus spp., and Cryptococcus spp. We explore the role of PTMs in fungal stress response and host adaptation, the use of PTMs to manipulate host cells and the immune system upon fungal invasion, and the importance of PTMs in conferring antifungal resistance. We also provide a critical view on the current knowledgebase, pose questions key to our understanding of the intricate roles of PTMs within fungal pathogens, and provide research opportunities to uncover new therapeutic strategies. Full article

(This article belongs to the Special Issue Systems Biology in Fungal Research)

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