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Journal of Enzyme Inhibition and... Dec 2020causes several fungal human diseases, mainly chromoblastomycosis, which is extremely difficult to treat. Several studies have shown that human immunodeficiency virus...
causes several fungal human diseases, mainly chromoblastomycosis, which is extremely difficult to treat. Several studies have shown that human immunodeficiency virus peptidase inhibitors (HIV-PIs) are attractive candidates for antifungal therapies. This work focused on studying the action of HIV-PIs on peptidase activity secreted by and their effects on fungal proliferation and macrophage interaction. We detected a peptidase activity from able to cleave albumin, sensitive to pepstatin A and HIV-PIs, especially lopinavir, ritonavir and amprenavir, showing for the first time that this fungus secretes aspartic-type peptidase. Furthermore, lopinavir, ritonavir and nelfinavir reduced the fungal growth, causing remarkable ultrastructural alterations. Lopinavir and ritonavir also affected the conidia-macrophage adhesion and macrophage killing. Interestingly, had its growth inhibited by ritonavir combined with either itraconazole or ketoconazole. Collectively, our results support the antifungal action of HIV-PIs and their relevance as a possible alternative therapy for fungal infections.
Topics: Antifungal Agents; Aspartic Acid Proteases; Carbamates; Dose-Response Relationship, Drug; Furans; HIV Protease Inhibitors; Humans; Lopinavir; Macrophages; Microbial Sensitivity Tests; Molecular Structure; Phialophora; Ritonavir; Structure-Activity Relationship; Sulfonamides
PubMed: 32037904
DOI: 10.1080/14756366.2020.1724994 -
Frontiers in Immunology 2022mutations are known to predispose patients to phaeohyphomycosis caused by different dematiaceous fungal species. In this study, we report for the first time a patient... (Comparative Study)
Comparative Study
mutations are known to predispose patients to phaeohyphomycosis caused by different dematiaceous fungal species. In this study, we report for the first time a patient of chromoblastomycosis caused by , who harbored mutation. Through a series of and studies, especially a comparative transcriptome study, we compared this case with our former patient suffering from phaeohyphomycosis caused by . We showed that is prone to forming sclerotic bodies both and in knockout mice, and has a stronger immunogenicity than . These data preliminary demonstrated that besides host defense, fungal specificity also contributed to the clinical phenotype in deficient patients with dematiaceous fungal infections.
Topics: Animals; CARD Signaling Adaptor Proteins; Candidiasis, Chronic Mucocutaneous; Chromoblastomycosis; Disease Susceptibility; Humans; Mice; Mice, Knockout; Phaeohyphomycosis; Transcriptome
PubMed: 36159827
DOI: 10.3389/fimmu.2022.984093 -
Frontiers in Plant Science 2019, a species characterized by rapid growth and high drought resistance, has been used widely for vegetative restoration of arid regions in Northwest China that are prone...
, a species characterized by rapid growth and high drought resistance, has been used widely for vegetative restoration of arid regions in Northwest China that are prone to desertification. Desert soil is typically deficient in available water and the alleviation of drought stress to host plants by endophytes could be an efficient strategy to increase the success of desert restoration. With the objective to seek more beneficial symbionts that can be used in the revegetation strategies, we addressed the question whether can benefit from inoculation by dark septate endophytes (DSEs) isolated from other desert plants. We investigated the influences of four non-host DSE strains ( sp., sp., sp., and ) isolated from other desert plants on the performance of under different soil water conditions. Differences in plant performance, such as plant growth, antioxidant enzyme activities, carbon, nitrogen, and phosphorous concentration under all the treatments, were examined. Four DSE strains could colonize the roots of successfully, and they established a positive symbiosis with the host plants depending on DSE species and water availability. The greatest benefits of DSE inoculation occurred in water stress treatment. Specifically, sp. and sp. improved the root biomass, total biomass, nutrient concentration, and antioxidant enzyme activities of host plants under water deficit conditions. These data contribute to the understanding of the ecological function of DSE fungi in drylands.
PubMed: 31354772
DOI: 10.3389/fpls.2019.00903 -
Mycologia 2019Timber durability is often assessed using small wood stakes exposed in direct soil contact, and the assessment generally emphasizes effects on wood rather than organisms...
Timber durability is often assessed using small wood stakes exposed in direct soil contact, and the assessment generally emphasizes effects on wood rather than organisms involved. Understanding fungal colonization patterns can help identify key decay agents under varying conditions and use these patterns to improve wood protection strategies. Fungal colonization of red alder (), Douglas-fir () heartwood/sapwood, and western redcedar () field stakes was assessed over 2 y in western Oregon. Spatiotemporal fungal community variations were identified via culturing and DNA sequencing, where 814 isolates were identified from 84 stakes. Forty-six ascomycete genera were identified, with , and species occurring most frequently. Twenty-three basidiomycete genera were identified, with and being the most common. Douglas-fir and western redcedar stakes contained the highest and lowest diversity levels, respectively, reflecting natural durability differences of these species. Fungal species abundance was higher below ground than in the above ground and groundline zones, likely reflecting more stable moisture regimes, proximity to soil-based fungi, and potential nutrient migration into wood beneath the soil surface. Ascomycetes were proportionally more abundant early in the exposure period, but basidiomycetes were also observed early in the process, and there appeared to be no consistent colonization pattern.
Topics: Alnus; Fungi; Microbiological Techniques; Mycobiome; Oregon; Pseudotsuga; Sequence Analysis, DNA; Spatio-Temporal Analysis; Thuja; Wood
PubMed: 31348726
DOI: 10.1080/00275514.2019.1631050 -
Enzyme and Microbial Technology Oct 2023ZEN lactone hydrolase (ZHD) can hydrolyze zearalenone (ZEN) to less or non-toxic product, providing an environment-friendly way for food or feeds-containing ZENs...
ZEN lactone hydrolase (ZHD) can hydrolyze zearalenone (ZEN) to less or non-toxic product, providing an environment-friendly way for food or feeds-containing ZENs detoxification. Here, a newly identified ZHD from Phialophora attinorum, annotated as Zhd11D, was characterized to exhibit highest activity against ZEN at pH 8.0 and 35 ℃ with a specific activity of 304.7 U/mg, which was far higher than most of the reported ZHDs. A nonspecific protein engineering method was introduced through fusing a segment of amphiphilic short peptide S1 at the N-terminus of Zhd11D, resulting in both improved activity (1.5-fold) and thermostability (2-fold at 40 ℃). Biochemical analysis demonstrated that self-aggregation caused by intermolecular interactions between S1 contributed to the improvement of the enzymatic properties of Zhd11D. Additionally, S1-Zhd11D showed a higher hydrolysis rate of ZEN than Zhd11D in peanut oil.
Topics: Zearalenone; Phialophora; Hydrolases; Lactones
PubMed: 37499311
DOI: 10.1016/j.enzmictec.2023.110286 -
Journal of Clinical Immunology Apr 2020Autosomal recessive (AR) CARD9 deficiency is an inherited immune disorder which results in impaired innate immunity against various fungi. Superficial and invasive... (Review)
Review
PURPOSE
Autosomal recessive (AR) CARD9 deficiency is an inherited immune disorder which results in impaired innate immunity against various fungi. Superficial and invasive fungal infections, mainly caused by Candida or Trichophyton species, are the hallmark of CARD9 deficiency. Together with the increasing number of CARD9-deficient patients reported, different pathogenic fungal species have been described such as Phialophora, Exophiala, Corynespora, Aureobasidium, and Ochroconis. Saprochaete capitata is an opportunistic infectious agent in immunocompromised patients and is a common cause of invasive fungal disease in patients with hematological malignancies. In this study, we investigated the causative genetic defect in a patient with S. capitata fungal infection which disseminated to lymph nodes and common bile duct.
METHODS
The identification of the isolated yeast strain was made by direct microscopic examination and confirmed by internal transcribed spacer (ITS) sequencing. We applied whole exome sequencing to search for the disease-causing mutation. Sanger sequencing was used to validate the mutation in the patient and his parents.
RESULTS
S. capitata was isolated from the biopsy specimen as the causative microorganism responsible for the invasive fungal disease in the patient. Whole exome sequencing revealed a homozygous c.883C > T, (p.Q295*) mutation in CARD9, confirmed by Sanger sequencing.
CONCLUSIONS
This is the first report of invasive Saprochaete infection associated with autosomal recessive (AR) CARD9 deficiency in the literature and thereby further extends the spectrum of fungal diseases seen in these patients.
Topics: Adolescent; CARD Signaling Adaptor Proteins; Candidiasis, Chronic Mucocutaneous; Cholestasis; Chromosome Disorders; Genes, Recessive; Humans; Immunocompromised Host; Invasive Fungal Infections; Iraq; Male; Saccharomycetales; Sequence Deletion; Exome Sequencing
PubMed: 32020378
DOI: 10.1007/s10875-020-00759-w -
Journal of Agricultural and Food... Feb 2023Zearalenone (ZEN) is an estrogenic mycotoxin most frequently found in cereals that can cause reproductive disorders in livestock and pose a severe threat to animal...
Zearalenone (ZEN) is an estrogenic mycotoxin most frequently found in cereals that can cause reproductive disorders in livestock and pose a severe threat to animal husbandry. In this study, we isolated a ZEN-degrading strain from soil and found that ZenH, a hydrolase, is responsible for the hydrolysis of ZEN through comparative proteomics and biochemical studies. ZenH exhibited the highest similarity with lactone hydrolase ZHD607 from at 21.52%. ZenH displayed maximal enzymatic activity at pH 7.0 and 55 °C with a Michaelis constant of 12.64 μM. The catalytic triad of ZenH was identified as S117-D142-H292 by molecular docking and site-directed mutagenesis. ZenH catalyzed the hydrolysis of ZEN to a novel metabolite, (,)-4-hydroxy-2-(10-hydroxy-6-oxoundec-1-en-1-yl)-7-oxabicyclo[4.2.0]octa-1,3,5-trien-8-one, which exhibited significantly lower estrogenic toxicity than ZEN. This study illustrates a novel ZEN-degrading enzyme and reveals a new degradation product. Furthermore, the enzyme showed good potential for detoxifying ZEN during food processing.
Topics: Animals; Zearalenone; Hydrolases; Molecular Docking Simulation; Mycotoxins; Biodegradation, Environmental
PubMed: 36701132
DOI: 10.1021/acs.jafc.2c06410 -
Microorganisms Apr 2020Dark septate endophytes (DSEs) are often trace element (TE)-tolerant fungi and are abundant in TE-polluted environments. The production of melanin, a black polymer found...
Dark septate endophytes (DSEs) are often trace element (TE)-tolerant fungi and are abundant in TE-polluted environments. The production of melanin, a black polymer found in cell walls, was hypothesized by several authors to play a role in the TE tolerance of DSEs. To test this hypothesis, we established a series of experiments using albino strains and melanin inhibitors and examined the responses to Cd and Zn. Six DSEs belonging to genera sp., sp. and , were evaluated. The strains mainly produced 1,8-dihydroxynaphthalene (DHN) melanin whereas 3,4-dihydroxyphenylalanin melanin was also synthetized. Cd and Zn decreased melanin synthesis in most of the strains. A reduction in melanin concentration in hyphae through the use of tricyclazole, an inhibitor of DHN-melanin synthesis, did not reduce the tolerance of the strains to Cd and Zn. Similarly, albino mutants of sp. were not more sensitive to Cd and Zn than the WT strain. Moreover, tricyclazole-treated colonies accumulated less Cd but more Zn compared to untreated colonies. The Cd and Zn contents of albino strains were variable and similar to that of the WT. The results suggest that melanin production is not an important functional trait that contributes to Cd and Zn tolerance, but might contribute to Cd accumulation.
PubMed: 32276491
DOI: 10.3390/microorganisms8040537 -
Frontiers in Immunology 2022-related inherited immune disorders are a major risk factor for chronic disseminated fungal infection. In addition to pathogens of and dermatophytes, the environmental...
-related inherited immune disorders are a major risk factor for chronic disseminated fungal infection. In addition to pathogens of and dermatophytes, the environmental opportunists of the black yeast-like fungi are relatively frequent in this patient cohort. Particularly the genus is overrepresented. We investigated two isolates of a strain of residing in a patient, sampled with a period of ten years apart. Genomes, melanization and antifungal susceptibility of progenitor and derived strains were compared, and potential adaptation to the host habitat was investigated with proteomic techniques using post-translational modification as a proxy. Global lactylation analysis was performed using high accuracy nano-LC-MS/MS in combination with enrichment of lactylated peptides from digested cell lysates, and subsequent peptide identification. The genome of the derived isolate had accumulated 6945 SNPs, of which 31 were detected in CDS. A large number of identified proteins were significantly enriched, e.g. in melanin biosynthesis. A total of 636 lactylation sites on 420 lactylated proteins were identified, which contained in 26 types of modification motifs. Lysine lactylation (Kla) was found in 23 constituent proteins of the ribosome, indicating an impact of Kla in protein synthesis. Twelve lactylated proteins participated in pathogenicity. A protein-protein interaction (PPI) network analysis suggested that protein lactylations are widely distributed influencing various biological processes. Our findings reveal widespread roles for lysine lactylation in regulating metabolism and melanin biosynthesis in black fungi. Several large rearrangements and inversions were observed in the genome, but genomic changes could not be linked to adaptation or to known clinically relevant properties of progenitor to derived isolate; antifungal susceptibility had largely remained unaltered.
Topics: Antifungal Agents; CARD Signaling Adaptor Proteins; Humans; Immune System Diseases; Lysine; Melanins; Phialophora; Protein Processing, Post-Translational; Proteomics; Tandem Mass Spectrometry
PubMed: 36003392
DOI: 10.3389/fimmu.2022.966457 -
Mycopathologia Jun 2021Phialophora verrucosa (P. verrucosa) is a pathogen that can cause chromoblastomycosis and phaeohyphomycosis. Recent evidence suggests that neutrophils can produce...
Phialophora verrucosa (P. verrucosa) is a pathogen that can cause chromoblastomycosis and phaeohyphomycosis. Recent evidence suggests that neutrophils can produce neutrophil extracellular traps (NETs) that can protect against invasive pathogens. As such, we herein explored the in vitro functional importance of P. verrucosa-induced NET formation. By assessing the co-localization of neutrophil elastase and DNA, we were able to confirm the formation of classical NETs entrapping P. verrucosa specimens. Sytox Green was then used to stain these NETs following neutrophil infection with P. verrucosa in order to quantify the formation of these extracellular structures. NET formation was induced upon neutrophil exposure to both live, UV-inactivated, and dead P. verrucosa fungi. The ability of these NETs to kill fungal hyphae and conidia was demonstrated through MTT and pouring plate assays, respectively. Overall, our results confirmed that P. verrucosa was able to trigger the production of NETs, suggesting that these extracellular structures may represent an important innate immune effector mechanism controlling physiological responses to P. verrucosa infection, thereby aiding in pathogen control during the acute phases of infection.
Topics: Extracellular Traps; Humans; Hyphae; Neutrophils; Phialophora
PubMed: 34013384
DOI: 10.1007/s11046-021-00554-0