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HDA-2 and the BLR complex regulate the transcription of ROS-related genes in response to H2O2 and menadione. Relative expressions of cat-3, sod-1, gst-1, and gpx genes in wt, Δblr-1, Δblr-2, and Δhda-2-2 strains under control conditions or exposed to 30 mM H2O2 (a to d) or 0.2 mM menadione (e to h) at the indicated times were determined. The tef-1 gene was used as a control to normalize the expression of ROS-related genes using the 2−ΔΔCT method. The graphs show the mean expression levels ± SD. The results are based on three repeats in two independent experiments.
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Importance:
Trichoderma atroviride is a free-living fungus commonly found in soil or colonizing plant roots, and is widely used as an agent in biocontrol as it parasites other fungi, stimulates plant growth, and induces the plant defense system. To survive in various environments, fungi constantly sense and respond to potentially threatening exter...
Citations
... "Classical"-Zn 2+ ion binding-fungal lysine deacetylases can be assigned to class I (Rpd3 family comprising the enzymes Rpd3 and Hos2) and class II (Hda1 family comprising the enzymes Hda1 and Hos3) HDACs, based on their sequence similarity to the respective Saccharomyces cerevisiae orthologues (11)(12)(13)(14)(15). Functional characterization of the class I HDAC Hda-2 in T. atroviride-the orthologue of S. cerevisiae Hos2-was described to regulate growth, conidiation, blue light perception, and oxidative stress response (16). In Aspergillus nidulans, the class II HDAC encoding gene hdaA is account able for the majority of HDAC activity (17), and its deletion led to the transcriptional activation of gene clusters for sterigmatocystin and penicillin production and a derepression of telomere-proximal secondary metabolite gene clusters (18). ...
... Sparse information is available on the functional role of HDACs in mycoparasitic fungi. Solely Hda-2, the orthologue of the class I HDAC HOS2 of S. cerevisiae, has been functionally characterized in T. atroviride to date and is involved in the regulation of growth, conidiation, blue-light perception, oxidative stress response (16), and VOC biosynthesis and in plant defense response against foliar fungal pathogens (31). ...
... HDACs are well known to differentially regulate the response to biotic and abiotic stress as well as the biosynthesis of various metabolites in fungi (9,10,16,(51)(52)(53)(54). Hda1, in particular, was described to affect the oxidative stress response in S. cerevisiae (55-57), A. nidulans (17,18), and P. chrysogenum (58) and drug resistance and antifungal susceptibility of S. cerevisiae (59) and C. albicans (35) as well as to differentially and globally govern the biosynthesis of several metabolites in A. fumigatus (19), F. fujikuroi (21,60), M. oryzae (20), and other fungi (14). ...
The mycoparasitic fungus Trichoderma atroviride is applied in agriculture as a biostimulant and biologic control agent against fungal pathogens that infest crop plants. Secondary metabolites are among the main agents determining the strength and progress of the mycoparasitic attack. However, expression of most secondary metabolism-associated genes requires specific cues, as they are silent under routine laboratory conditions due to their maintenance in an inactive heterochromatin state. Therefore, histone modifications are crucial for the regulation of secondary metabolism. Here, we functionally investigated the role of the class II histone deacetylase encoding gene hda1 of T. atroviride by targeted gene deletion, phenotypic characterization, and multi-omics approaches. Deletion of hda1 did not result in obvious phenotypic alterations but led to an enhanced inhibitory activity of secreted metabolites and reduced mycoparasitic abilities of T. atroviride against the plant-pathogenic fungi Botrytis cinerea and Rhizoctonia solani. The ∆hda1 mutants emitted altered amounts of four volatile organic compounds along their development, produced different metabolite profiles upon growth in liquid culture, and showed a higher susceptibility to oxidative and osmotic stress. Moreover, hda1 deletion affected the expression of several notable gene categories such as polyketide synthases, transcription factors, and genes involved in the HOG MAPK pathway.
IMPORTANCE
Histone deacetylases play crucial roles in regulating chromatin structure and gene transcription. To date, classical—Zn²⁺ dependent—fungal histone deacetylases are divided into two classes, of which each comprises orthologues of the two sub-groups Rpd3 and Hos2 and Hda1 and Hos3 of yeast, respectively. However, the role of these chromatin remodelers in mycoparasitic fungi is poorly understood. In this study, we provide evidence that Hda1, the class II histone deacetylases of the mycoparasitic fungus Trichoderma atroviride, regulates its mycoparasitic activity, secondary metabolite biosynthesis, and osmotic and oxidative stress tolerance. The function of Hda1 in regulating bioactive metabolite production and mycoparasitism reveals the importance of chromatin-dependent regulation in the ability of T. atroviride to successfully control fungal plant pathogens.
... In Trichoderma-plant interactions, the histone deacetylase HDA-2 is required for the root colonization process and is necessary to promote plant growth of Arabidopsis thaliana (Estrada-Rivera et al., 2019). As HDA2 is involved in dealing with oxidative stress and ROS in T. atroviride (Osorio-Concepción et al., 2017), a strain lacking this protein may not be able to properly respond to plant defense and hence lose its beneficial effect. Trichoderma species cause substantial changes at molecular and biochemical levels when they interact with roots. ...
Trichoderma spp. are free-living fungi present in virtually all terrestrial ecosystems. These soil fungi can stimulate plant growth and increase plant nutrient acquisition of macro-and micronutrients and water uptake. Generally, plant growth promotion by Trichoderma is a consequence of the activity of potent fungal signaling metabolites diffused in soil with hormone-like activity, including indolic compounds as indole-3-acetic acid (IAA) produced at concentrations ranging from 14 to 234 μg l-1 , and volatile organic compounds such as sesquiterpene iso-prenoids (C 15), 6-pentyl-2H-pyran-2-one (6-PP) and ethylene (ET) produced at levels from 10 to 120 ng over a period of six days, which in turn, might impact plant endogenous signaling mechanisms orchestrated by plant hormones. Plant growth stimulation occurs without the need of physical contact between both organisms and/or during root colonization. When associated with plants Trichoderma may cause significant biochemical changes in plant content of carbohydrates, amino acids, organic acids and lipids, as detected in Arabidopsis thaliana, maize (Zea mays), tomato (Lycopersicon esculentum) and barley (Hordeum vulgare), which may improve the plant health status during the complete life cycle. Trichoderma-induced plant beneficial effects such as mechanisms of defense and growth are likely to be inherited to the next generations. Depending on the environmental conditions perceived by the fungus during its interaction with plants, Trichoderma can reprogram and/or activate molecular mechanisms commonly modulated by IAA, ET and abscisic acid (ABA) to induce an adaptative physiological response to abiotic stress, including drought, salinity, or environmental pollution. This review, provides a state of the art overview focused on the canonical mechanisms of these beneficial fungi involved in plant growth promotion traits under different environmental scenarios and shows new insights on Trichoderma metabolites from different chemical classes that can modulate specific plant growth aspects. Also, we suggest new research directions on Trichoderma spp. and their secondary metabolites with biological activity on plant growth.
... Similarly, in this work Arabidopsis roots showed reduced CFUs of Δtbrg-1, probably because it is incapable of coping with the hostile environment inside the host plant. In this regard a mutant in the hda-2 gene, which codes for a histone deacetylase class I, shows low level of cellular detoxification-and ROS-related genes, which parallels with low root colonization and high sensibility to ROS (Estrada-Rivera et al., 2019;Osorio-Concepción et al., 2017). An alternative explanation is that Δtbrg-1 could be affected in the expression of colonization factors, such as hydrophobins (Guzmán-Guzmán et al., 2017), swollenins (Brotman et al., 2008) and endopolygalacturonases (Morán-Diez et al., 2009). ...
... Histone acetylation can affect the biosynthesis of fungal SMs. The study by Osorio-concepción et al. found that the histone deacetylase HDA-2 of Trichoderma atroviride was induced by light [131]. These results indicate that light can regulate fungal secondary metabolism through epigenetic regulation. ...
Fungi have evolved unique metabolic regulation mechanisms for adapting to the changing environments. One of the key features of fungal adaptation is the production of secondary metabolites (SMs), which are essential for survival and beneficial to the organism. Many of these SMs are produced in response to the environmental cues, such as light. In all fungal species studied, the Velvet complex transcription factor VeA is a central player of the light regulatory network. In addition to growth and development, the intensity and wavelength of light affects the formation of a broad range of secondary metabolites. Recent studies, mainly on species of the genus Aspergillus, revealed that the dimer of VeA-VelB and LaeA does not only regulate gene expression in response to light, but can also be involved in regulating production of SMs. Furthermore, the complexes have a wide regulatory effect on different types of secondary metabolites. In this review, we discussed the role of light in the regulation of fungal secondary metabolism. In addition, we reviewed the photoreceptors, transcription factors, and signaling pathways that are involved in light-dependent regulation of secondary metabolism. The effects of transcription factors on the production of secondary metabolites, as well as the potential applications of light regulation for the production of pharmaceuticals and other products were discussed. Finally, we provided an overview of the current research in this field and suggested potential areas for future research.
... The acetylation of histone proteins at lysine residues is a highly reversible and dynamic process that involves the antagonistic functions of histone/lysine acetyltransferase (HATs/KATs) and histone deacetylases (HDACs) (Seto and Yoshida, 2014;Osorio-concepción and Cristóbal-mondragón, 2017). Restricted to eukaryotes, histone deacetylases (HDACs) share similarity to acetylpolyamine amidohydrolases of prokaryotes. ...
... The global transcriptional studies led to the identification of the hda-2 gene in T. atroviride (orthologous hda-2 and HOS2 genes of N. crassa and Saccharomyces cerevisiae, respectively) that encodes class I HDAC and are induced upto 6-fold upon exposure to blue light (Osorio- Concepción et al., 2017). hda-2 expression is BLR-1 dependent responsible for the expression of initial and late light-responsive genes such as blr-1 and others (Osorio-Concepción et al., 2017). ...
... The global transcriptional studies led to the identification of the hda-2 gene in T. atroviride (orthologous hda-2 and HOS2 genes of N. crassa and Saccharomyces cerevisiae, respectively) that encodes class I HDAC and are induced upto 6-fold upon exposure to blue light (Osorio- Concepción et al., 2017). hda-2 expression is BLR-1 dependent responsible for the expression of initial and late light-responsive genes such as blr-1 and others (Osorio-Concepción et al., 2017). HDA-2 of T. atroviride acts as a key regulator that regulates multiple responses such as ability to root colonization in Arabidopsis, trigger SAR and ISR, impaired VOCs metabolic activity, blue-light perception, conidiation and oxidative stresses (Estrada-rivera et al., 2019;Osorio-Concepción et al., 2017) (Fig. 3A). ...
Since the initial finding of Trichoderma as a biocontrol agent, efforts have been largely focused on understanding the role of glycosyl hydrolases and antibiotics in mycoparasitism, plant pathogen suppression and other plant growth promotion attributes. However, comparatively less attention has been given for reviewing the role of Trichoderma-derived molecules in plant immunity. Microbial derived molecular signatures are well known for the induction of systemic resistance in plants. In general, the molecules from non-pathogenic microorganisms, activate the plant's immune response via induced systemic response (ISR) that is driven through jasmonic acid (JA) / ethylene (ET) pathways whereas the signature molecules of pathogens origin, induce systemic acquired resistance (SAR) which is driven by salicylic acid (SA). The role of Trichoderma, in triggering the plant immunity has been studied in isolation both at local and systemic level. In this context, various signature molecules from Trichoderma and their roles in activating the plant immune responses have been identified. The elicitors such as Epl1 from Trichoderma through synergistic action, involving both JA / ET as well as SA primed systemic resistance. Furthermore, histone modification system from endophytic strain of Trichoderma through its epigenetic modification of histone proteins have been explored for modulating the expression of genes. The recent experimental studies have unraveled new players of Trichoderma induced systemic resistance with their probable role in SAR as well ISR mediated response. Here, we have described the complexity of biological repertoire and multifaceted aspects of Trichoderma in mediating the plant immune response.
... These results suggested that Set3/Hos2 histone deacetylase has previously unrecognized functions in the dynamic deposition or remodeling of nucleosomes containing H2A.Z. A recent study identified HDA-2 as a positive regulator for cat-3 transcription in Trichoderma atroviride (39). However, it is not clear whether HDA-2 is involved in regulation of cat-3 gene expression in N. crassa. ...
... As a histone deacetylase, we found that HDA-2containing complex positively regulates cat-3 transcription in N. crassa. In agreement with this result, HDA-2 was identified as a positive regulator for cat-3 transcription in Trichoderma atroviride (39). In yeast, Hos2 is important for activation of GAL1 and INO1 genes through binding to the coding regions of genes (25). ...
Clearance of reactive oxygen species (ROS) is critical to the survival of aerobic organisms. In the model filamentous fungus Neurospora crassa , catalase-3 ( cat-3 ) expression is activated in response to H 2 O 2 -induced ROS stress.
... About 30-fold increase in clr3 expression was observed in the wild-type strain after 60 min of exposure to 5 mM H2O2, indicating that clr3 plays an important role in positively regulating the antioxidant defense system of P. brasilianum against H2O2. Similar results were observed in T. atroviride, in which the expression of the histone deacetylase-encoding gene hda-2 was also increased under the influence of H2O2 and menadione [40]. ...
Most of the biosynthetic gene clusters (BGCs) found in microbes are silent under standard laboratory cultivation conditions due to the lack of expression triggering stimuli, representing a considerable drawback in drug discovery. To access the full biosynthetic potential, studies towards the activation of cryptic BGCs are essential. Histone acetylation status is an important regulator of chromatin structure, which impacts cell physiology and the expression of BGCs. In this study, clr3, a gene encoding a histone deacetylase in Penicillium brasilianum LaBioMMi 136, is deleted and associated phenotypic and metabolic changes are evaluated. The results indicate reduced growth under oxidative stress conditions in the ∆clr3 strain, higher intracellular reactive oxygen species (ROS) levels, and a different transcriptional profile of 13 ROS-related genes of both strains under basal and ROS-induced conditions. Moreover, the production of 14 secondary metabolites, including austin-related meroterpenoids, brasiliamides, verruculogen, penicillic acid, and cyclodep-sipeptides was evaluated in the ∆clr3 strain, most of them being reduced. Accordingly, the addition of epigenetic modulators responsible for HDAC inhibition into P. brasilianum's growth media also culminated in the reduction in secondary metabolite production. The results suggest that Clr3 plays an essential role in secondary metabolite biosynthesis in P. brasilianum, thus offering new strategies for the regulation of natural product synthesis by assessing chromatin modification.
... (Schmoll et al. 2010), which induces peptaibol release that enhances their antagonistic efficiency. Further, Osorio-Concepción et al. (2017) indicated that in T. atroviride the blue-light regulator (BLR) proteins BLR-1 and BLR-2 regulate several important activities in the cell including gene transcription and conidial production. Mechanical injury to the colonies provokes a stress response in mycelia that induces NADPH oxidase-dependent reactive oxygen species production and enhancement of calcium signalling mechanisms to trigger the production of conidia (Hernández-Oñate et al. 2012). ...
Background
Species belonging to the genus Trichoderma are considered as one of the most potential biocontrol agents which can be readily collected from soil and found effective against various fungal and bacterial diseases. In rice-growing areas, the major fungal pathogens affecting rice production include Rhizoctonia solani causing sheath blight and Sclerotium oryzae causing stem rot disease of rice. Due to the lack of resistant varieties and detrimental effects of chemicals, biocontrol gives a good opportunity to manage the diseases efficiently in a sustainable manner.
Main body
Trichoderma spp. from native rice rhizosphere soil were examined for their antagonistic efficiency to supress the two soil-borne rice pathogens, viz., R. solani and S. oryzae . Morphological, biochemical and molecular characterisation of the isolates led to the identification of species as T. asperellum . The isolates of Trichoderma spp. were found to be positive to IAA release and phosphate solubilisation and were screened against R. solani and S. oryzae in vitro and in vivo in pots under glass house conditions. Regression analysis indicated a positive correlation between the amount of chlamydospores produced by T. asperellum and their antagonistic potential against the two pathogens. Exposure to external stimuli, viz., light, injury and nitrogen sources in culture media triggered increased conidiation in Trichoderma isolates. Among the four isolates studied, Trichoderma asperellum IIRRCK1 (TAIK-1) was found to be the most effective in improving plant growth in rice and highly antagonistic against R. solani and S. oryzae . Sorghum grain was found to be the most suitable among different organic substrates studied to provide better growth and viability of TAIK-1 and improved the efficiency of the seed treatment and soil application. External stimuli in the form of near UV blue light, mechanical injury to the colonies and nitrogen source added to the culture media help in faster conidiation of Trichoderma .
Conclusion
Strain TAIK-1 showed strong competitive and antagonistic activities against fungal soil-borne pathogens, in addition with promoting healthy growth and development of rice plants. This can be a suitable and safe alternative to chemical management in the rice fields for long-term scenario.
... In many molds, including Trichoderma spp., conidiophores are not evenly distributed on the colony surface but appear in pustules or form characteristic conidial rings in response to circadian rhythms [44,45] or other stimuli [46]. We showed that in Trichoderma colonies, the emergence of such conidiation hot spots starts with the intracellular accumulation of HFBs. ...
Higher fungi can rapidly produce large numbers of spores suitable for aerial dispersal. The efficiency of the dispersal and spore resilience to abiotic stresses correlate with their hydrophobicity provided by the unique amphiphilic and superior surface-active proteins–hydrophobins (HFBs)–that self-assemble at hydrophobic/hydrophilic interfaces and thus modulate surface properties. Using the HFB-enriched mold Trichoderma (Hypocreales, Ascomycota) and the HFB-free yeast Pichia pastoris (Saccharomycetales, Ascomycota), we revealed that the rapid release of HFBs by aerial hyphae shortly prior to conidiation is associated with their intracellular accumulation in vacuoles and/or lipid-enriched organelles. The occasional internalization of the latter organelles in vacuoles can provide the hydrophobic/hydrophilic interface for the assembly of HFB layers and thus result in the formation of HFB-enriched vesicles and vacuolar multicisternal structures (VMSs) putatively lined up by HFBs. These HFB-enriched vesicles and VMSs can become fused in large tonoplast-like organelles or move to the periplasm for secretion. The tonoplast-like structures can contribute to the maintenance of turgor pressure in aerial hyphae supporting the erection of sporogenic structures (e.g., conidiophores) and provide intracellular force to squeeze out HFB-enriched vesicles and VMSs from the periplasm through the cell wall. We also show that the secretion of HFBs occurs prior to the conidiation and reveal that the even spore coating of HFBs deposited in the extracellular matrix requires microscopic water droplets that can be either guttated by the hyphae or obtained from the environment. Furthermore, we demonstrate that at least one HFB, HFB4 in T . guizhouense , is produced and secreted by wetted spores. We show that this protein possibly controls spore dormancy and contributes to the water sensing mechanism required for the detection of germination conditions. Thus, intracellular HFBs have a range of pleiotropic functions in aerial hyphae and spores and are essential for fungal development and fitness.
... gene expression [8]. However, in some circumstances gene repression and activation require HAT and HDAC, respectively, as shown in some reports [15][16][17]. ...
Histone deacetylase inhibitors (HDACi) are cancer therapeutics that operate at the epigenetic level and which have recently gained wide attention. However, the applications of HDACi are generally hindered by their poor physicochemical characteristics and unfavorable pharmacokinetic profile. Inspired by the approved nanomedicine-based drugs in the market, nanocarriers could provide a resort to circumvent the limitations imposed by HDACi. Enhanced tumor targeting, improved cellular uptake and reduced toxicity are major advantages offered by HDACi-loaded nanoparticles. More importantly, site-specific drug delivery can be achieved via engineered stimuli-responsive nanosystems. In this review we elucidate the anticancer mechanisms of HDACi and their structure–activity relationships, with a special focus on their nanomedicine-based delivery, different drug loading concepts and their implications.
