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Virulence Dec 2023is an important opportunistic pathogenic fungus that frequently causes serious systemic infection in humans. Due to the vital roles of biofilm formation and the...
is an important opportunistic pathogenic fungus that frequently causes serious systemic infection in humans. Due to the vital roles of biofilm formation and the yeast-to-hypha transition in the infection process, we have selected a series of diaryl chalcogenides and tested their efficacy against SC5314 pathogenicity by the inhibition of biofilm formation and the yeast-to-hypha transition. The compounds 5-sulfenylindole and 5-selenylindole were found to have excellent abilities to inhibit both biofilm formation and hyphal formation in SC5314. Intriguingly, the two leading compounds also markedly attenuated SC5314 virulence in human cell lines and mouse infection models at micromolar levels. Furthermore, our results showed that the presence of the compounds at 100 µM resulted in a marked decrease in the expression of genes involved in the cAMP-PKA and MAPK pathways in SC5314. Intriguingly, the compounds 5-sulfenylindole and 5-selenylindole not only attenuated the cytotoxicity of species strains but also showed excellent synergistic effects with antifungal agents against the clinical drug-resistant strain HCH12. The compound 5-sulfenylindole showed an obvious advantage over fluconazole as it could also restore the composition and richness of the intestinal microbiota in mice infected by . Together, these results suggest that diaryl chalcogenides can potentially be designed as novel clinical therapeutic agents against infection. The diaryl chalcogenides of 5-sulfenylindole and 5-selenylindole discovered in this study can provide new direction for developing antifungal agents against infection.
Topics: Mice; Humans; Animals; Candida albicans; Antifungal Agents; Virulence; Candidiasis; Fluconazole; Hyphae; Biofilms
PubMed: 37771181
DOI: 10.1080/21505594.2023.2265012 -
Ecology and Evolution Aug 2023The large amount of dead plant biomass caused by the final extinction events triggered a fungi proliferation that mostly differentiated into saprophytes degrading... (Review)
Review
The large amount of dead plant biomass caused by the final extinction events triggered a fungi proliferation that mostly differentiated into saprophytes degrading organic matter; others became parasites, predators, likely commensals, and mutualists. Among the last, many have relationships with ants, the most emblematic seen in the Neotropical myrmicine Attina that cultivate Basidiomycota for food. Among them, leaf-cutting, fungus-growing species illustrate an ecological innovation because they grow fungal gardens from fresh plant material rather than arthropod frass and plant debris. Myrmecophytes shelter "plant-ants" in hollow structures, the domatia, whose inner walls are lined with thin-walled Ascomycota hyphae that, in certain cases, are eaten by the ants, showing a form of convergence. Typically, these Ascomycota have antibacterial properties illustrating cases of farming for protection. Ant gardens, or mutualistic associations between certain ant species and epiphytes, shelter endophytic fungi that promote the growth of the epiphytes. Because the cell walls of certain Ascomycota hyphae remain sturdy after the death of the mycelium, they form resistant fibers used by ants to reinforce their constructions (e.g., galleries, shelters for tended hemipterans, and carton nests). Thus, we saw cases of "true" fungal agriculture involving planting, cultivating, and harvesting Basidiomycota for food with Attina. A convergence with "plant-ants" feeding on Ascomycota whose antibacterial activity is generally exploited (i.e., farming for protection). The growth of epiphytes was promoted by endophytic fungi in ant gardens. Finally, farming for structural materials occurred with, in one case, a leaf-cutting, fungus-growing ant using Ascomycota fibers to reinforce its nests.
PubMed: 37529578
DOI: 10.1002/ece3.10386 -
Journal of Fungi (Basel, Switzerland) Oct 2023Light represents a powerful signal for the regulation of virulence in many microbial pathogens. is the most virulent species causing brown rot in stone fruit crops. To...
Light represents a powerful signal for the regulation of virulence in many microbial pathogens. is the most virulent species causing brown rot in stone fruit crops. To understand the influence of light on , we measured the effect of white light and photoperiods on the colonial growth and sporulation of the model strain 38C on solid cultures. Searches in the 38C genome predicted a complete set of genes coding for photoreceptors possibly involved in the perception of all ranges of wavelengths. Since white light had an obvious negative effect on vegetative growth and the asexual development of 38C on potato dextrose agar, we studied how light influences photoresponse genes in during early peach infection and in liquid culture. The transcriptomes were analyzed in "Red Jim" nectarines infected by 38C and subjected to light pulses for 5 min and 14 h after 24 h of incubation in darkness. Specific light-induced genes were identified. Among these, we confirmed in samples from infected fruit or synthetic media that blue light photoreceptor was among the highest expressed genes. An unknown gene, , coding for a small protein conserved in many families of Ascomycota phylum, was also highly induced by light. In contrast, a range of well-known photoreceptors displayed a low transcriptional response to light in from nectarines but not on the pathogen mycelium growing in liquid culture media for 6 days.
PubMed: 37888244
DOI: 10.3390/jof9100988 -
Biotechnology Reports (Amsterdam,... Sep 2023Biocomposites create attractive alternatives to match packing needs with available agricultural residues. Growing native fungal strains developed a mycelium biocomposite...
Biocomposites create attractive alternatives to match packing needs with available agricultural residues. Growing native fungal strains developed a mycelium biocomposite over a mixture of Peach Palm Fruit Peel Flour and Sugar Cane Bagasse Wet Dust. A methodology was proposed to analyze their main characteristics: 1) morphological, 2) chemical, and 3) biodegradability. 1) SEM analysis evidenced the structural change of the dried pressed material and mycelium morphology for both species. 2) The ratio lignin:carbohydrate showed that degrades the cellulose-hemicellulose fraction of the substrate at a higher rate than , and 3) the curve BMP indicated that these materials are readily biodegradable with a maximum yield of 362,50 mL biogas/g VS. An innovative tangible valorization strategy based on mass balances is also presented: from just 50 kg of peel flour, up to 1840 units can be manufactured, which could pave the way for a more sustainable future.
PubMed: 37448784
DOI: 10.1016/j.btre.2023.e00807 -
International Journal of Molecular... Aug 2023is a devastating fungal pathogen that causes severe crop losses worldwide. It is of vital importance to understand its pathogenic mechanism for disease control. Through...
is a devastating fungal pathogen that causes severe crop losses worldwide. It is of vital importance to understand its pathogenic mechanism for disease control. Through a forward genetic screen combined with next-generation sequencing, a putative protein kinase, Cak1, was found to be involved in the growth and pathogenicity of . Knockout and complementation experiments confirmed that deletions in caused defects in mycelium and sclerotia development, as well as appressoria formation and host penetration, leading to complete loss of virulence. These findings suggest that Cak1 is essential for the growth, development, and pathogenicity of . Therefore, Cak1 could serve as a potential target for the control of infection through host-induced gene silencing (HIGS), which could increase crop resistance to the pathogen.
Topics: Virulence; Ascomycota; Gene Silencing; High-Throughput Nucleotide Sequencing
PubMed: 37628791
DOI: 10.3390/ijms241612610 -
Fungal Biology and Biotechnology Nov 2023Asexually developed fungal spores (conidia) are key for the massive proliferation and dispersal of filamentous fungi. Germination of conidia and subsequent formation of...
BACKGROUND
Asexually developed fungal spores (conidia) are key for the massive proliferation and dispersal of filamentous fungi. Germination of conidia and subsequent formation of a mycelium network give rise to many societal problems related to human and animal fungal diseases, post-harvest food spoilage, loss of harvest caused by plant-pathogenic fungi and moulding of buildings. Conidia are highly stress resistant compared to the vegetative mycelium and therefore even more difficult to tackle.
RESULTS
In this study, complementary approaches are used to show that accumulation of mannitol and trehalose as the main compatible solutes during spore maturation is a key factor for heat resistance of conidia. Compatible solute concentrations increase during conidia maturation, correlating with increased heat resistance of mature conidia. This maturation only occurs when conidia are attached to the conidiophore. Moreover, conidia of a mutant Aspergillus niger strain, constructed by deleting genes involved in mannitol and trehalose synthesis and consequently containing low concentrations of these compatible solutes, exhibit a sixteen orders of magnitude more sensitive heat shock phenotype compared to wild-type conidia. Cultivation at elevated temperature results in adaptation of conidia with increased heat resistance. Transcriptomic and proteomic analyses revealed two putative heat shock proteins to be upregulated under these conditions. However, conidia of knock-out strains lacking these putative heat shock proteins did not show a reduced heat resistance.
CONCLUSIONS
Heat stress resistance of fungal conidia is mainly determined by the compatible solute composition established during conidia maturation. To prevent heat resistant fungal spore contaminants, food processing protocols should consider environmental conditions stimulating compatible solute accumulation and potentially use compatible solute biosynthesis as a novel food preservation target.
PubMed: 37957766
DOI: 10.1186/s40694-023-00168-9 -
International Journal of Molecular... Oct 2023Fifty-two kinds of '-phenylhydrazides were successfully designed and synthesized. Their antifungal activity in vitro against five strains of () was evaluated. All...
Fifty-two kinds of '-phenylhydrazides were successfully designed and synthesized. Their antifungal activity in vitro against five strains of () was evaluated. All prepared compounds showed varying degrees of antifungal activity against and their MIC (the concentration of tested compounds when their inhibition rate was at 80%), TAI (total activity index), and TSI (total susceptibility index) were calculated. The inhibitory activities of 27/52 compounds against fluconazole-resistant fungi 4395 and 5272 were much better than those of fluconazole. The MIC values of 14/52 compounds against fluconazole-resistant fungus 5122 were less than 4 μg/mL, so it was the most sensitive fungus (TSI = 12.0). showed the best inhibitory activity against SC5314, 4395, and 5272 (MIC = 1.9, 4.0, and 3.7 μg/mL). The antifungal activities of and against four strains of fluconazole-resistant fungi were better than those of fluconazole. The TAI values of (2.71), (2.13), and (2.25) are the highest. Further exploration of antifungal mechanisms revealed that the fungus treated with compound produced free radicals and reactive oxygen species, and their mycelium morphology was damaged. In conclusion, the '-phenylhydrazide scaffold showed potential in the development of antifungal lead compounds. Among them, , , and demonstrated particularly promising antifungal activity and held potential as novel antifungal agents.
Topics: Antifungal Agents; Fluconazole; Microbial Sensitivity Tests; Phenylhydrazines; Candida albicans
PubMed: 37894800
DOI: 10.3390/ijms242015120 -
Polymers Sep 2023Electrospun nanofiber mats have a high specific surface area and very small pores which can be tailored by the spinning process. They are thus highly suitable as filters...
Electrospun nanofiber mats have a high specific surface area and very small pores which can be tailored by the spinning process. They are thus highly suitable as filters for small particles and molecules, such as organic dyes. On the other hand, they are usually very thin and thus have low mechanical properties. As a potential reinforcement, mycelium of was grown on poly(acrylonitrile) nanofiber mats and thermally solidified after fully covering the nanofiber mats. This study investigates whether the filtration efficiency of the nanofiber mats is altered by the mycelium growing through it and whether the mechanical properties of the nanofibrous filters can be improved in this way. The study shows fast and reliable growth of the mycelium on the nanofiber mats and high filtration efficiency for astra blue and chlorophyll, while indigo carmine showed only very low filtration efficiency of up to 20%. For chlorophyll and safranin, membranes with mycelium showed higher filtration than pure nanofiber mats. In diffusion cell tests, especially astra blue was strongly adsorbed on the membranes with mycelium.
PubMed: 37836000
DOI: 10.3390/polym15193951 -
MBio Aug 2023An important feature associated with pathogenicity is its ability to switch between yeast and hyphal forms, a process in which CaRas1 plays a key role. CaRas1 is...
An important feature associated with pathogenicity is its ability to switch between yeast and hyphal forms, a process in which CaRas1 plays a key role. CaRas1 is activated by the guanine nucleotide exchange factor (GEF) CaCdc25, triggering hyphal growth-related signaling pathways through its conserved GTP-binding (G)-domain. An important function in hyphal growth has also been proposed for the long hypervariable region downstream the G-domain, whose unusual content of polyglutamine stretches and Q/N repeats make CaRas1 unique within Ras proteins. Despite its biological importance, both the structure of CaRas1 and the molecular basis of its activation by CaCdc25 remain unexplored. Here, we show that CaRas1 has an elongated shape and limited conformational flexibility and that its hypervariable region contains helical structural elements, likely forming an intramolecular coiled-coil. Functional assays disclosed that CaRas1-activation by CaCdc25 is highly efficient, with activities up to 2,000-fold higher than reported for human GEFs. The crystal structure of the CaCdc25 catalytic region revealed an active conformation for the α-helical hairpin, critical for CaRas1-activation, unveiling a specific region exclusive to CTG-clade species. Structural studies on CaRas1/CaCdc25 complexes also revealed an interaction surface clearly distinct from that of homologous human complexes. Furthermore, we identified an inhibitory synthetic peptide, prompting the proposal of a key regulatory mechanism for CaCdc25. To our knowledge, this is the first report of specific inhibition of the CaRas1-activation via targeting its GEF. This, together with their unique pathogen-structural features, disclose a set of novel strategies to specifically block this important virulence-related mechanism. IMPORTANCE is the main causative agent of candidiasis, the commonest fungal infection in humans. The eukaryotic nature of and the rapid emergence of antifungal resistance raise the challenge of identifying novel drug targets to battle this prevalent and life-threatening disease. CaRas1 and CaCdc25 are key players in the activation of signaling pathways triggering multiple virulence traits, including the yeast-to-hypha interconversion. The structural similarity of the conserved G-domain of CaRas1 to those of human homologs and the lack of structural information on CaCdc25 has impeded progress in targeting these proteins. The unique structural and functional features for CaRas1 and CaCdc25 presented here, together with the identification of a synthetic peptide capable of specifically inhibiting the GEF activity of CaCdc25, open new possibilities to uncover new antifungal drug targets against virulence.
Topics: Humans; Candida albicans; Antifungal Agents; Candidiasis; Signal Transduction; Guanine Nucleotide Exchange Factors; Fungal Proteins; Hyphae
PubMed: 37526476
DOI: 10.1128/mbio.00638-23 -
Scientific Reports Nov 2023Gradient porous structures (GPS) are characterized by structural variations along a specific direction, leading to enhanced mechanical and functional properties compared...
Gradient porous structures (GPS) are characterized by structural variations along a specific direction, leading to enhanced mechanical and functional properties compared to homogeneous structures. This study explores the potential of mycelium, the root part of a fungus, as a biomaterial for generating GPS. During the intentional growth of mycelium, the filamentous network undergoes structural changes as the hyphae grow away from the feed substrate. Through microstructural analysis of sections obtained from the mycelium tissue, systematic variations in fiber characteristics (such as fiber radii distribution, crosslink density, network density, segment length) and pore characteristics (including pore size, number, porosity) are observed. Furthermore, the mesoscale mechanical moduli of the mycelium networks exhibit a gradual variation in local elastic modulus, with a significant change of approximately 50% across a 30 mm thick mycelium tissue. The structure-property analysis reveals a direct correlation between the local mechanical moduli and the network crosslink density of the mycelium. This study presents the potential of controlling growth conditions to generate mycelium-based GPS with desired functional properties. This approach, which is both sustainable and economically viable, expands the applications of mycelium-based GPS to include filtration membranes, bio-scaffolds, tissue regeneration platforms, and more.
Topics: Tissue Scaffolds; Porosity; Biocompatible Materials; Elastic Modulus; Mycelium
PubMed: 37935723
DOI: 10.1038/s41598-023-45842-5