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MSphere May 2024is the leading cause of severe mold infections in immunocompromised patients. This common fungus possesses innate attributes that allow it to evade the immune system,...
is the leading cause of severe mold infections in immunocompromised patients. This common fungus possesses innate attributes that allow it to evade the immune system, including its ability to survive the high copper (Cu) levels in phagosomes. Our previous work has revealed that under high Cu levels, the transcription factor AceA is activated, inducing the expression of the copper exporter CrpA to expel excess Cu. To identify additional elements in Cu resistance, we evolved wild-type and mutant Δ or Δ strains under increasing Cu concentrations. Sequencing of the resultant resistant strains identified both shared and unique evolutionary pathways to resistance. Reintroduction of three of the most common mutations in genes encoding Pma1 (plasma membrane H-ATPase), Gcs1 (glutamate cysteine-ligase), and Cpa1 (carbamoyl-phosphate synthetase), alone and in combination, into wild-type confirmed their additive role in conferring Cu resistance. Detailed analysis indicated that the mutation L424I preserves Pma1 H-ATPase activity under high Cu concentrations and that the mutation A37V confers a survival advantage to conidia in the presence of Cu. Interestingly, simultaneous mutations of all three genes did not alter virulence in infected mice. Our work has identified novel Cu-resistance pathways and provides an evolutionary approach for dissecting the molecular basis of adaptation to diverse environmental challenges.IMPORTANCE is the most common mold infecting patients with weakened immunity. Infection is caused by the inhalation of mold spores into the lungs and is often fatal. In healthy individuals, spores are engulfed by lung immune cells and destroyed by a combination of enzymes, oxidants, and high levels of copper. However, the mold can protect itself by pumping out excess copper with specific transporters. Here, we evolved under high copper levels and identified new genetic mutations that help it resist the toxic effects of copper. We studied how these mutations affect the mold's ability to resist copper and how they impact its ability to cause disease. This is the first such study in a pathogenic mold, and it gives us a better understanding of how it manages to bypass our body's defenses during an infection.
PubMed: 38814077
DOI: 10.1128/msphere.00253-24 -
Frontiers in Microbiology 2024Cancer remains a significant global health challenge, claiming nearly 10 million lives in 2020 according to the World Health Organization. In the quest for novel... (Review)
Review
Cancer remains a significant global health challenge, claiming nearly 10 million lives in 2020 according to the World Health Organization. In the quest for novel treatments, fungi, especially species, have emerged as a valuable source of bioactive compounds with promising anticancer properties. This study conducts a comprehensive bibliometric analysis to map the research landscape of in oncology, examining publications from 1982 to the present. We observed a marked increase in research activity starting in 2000, with a notable peak from 2005 onwards. The analysis identifies key contributors, including Mohamed GG, who has authored 15 papers with 322 citations, and El-Sayed Asa, with 14 papers and 264 citations. Leading countries in this research field include India, Egypt, and China, with King Saud University and Cairo University as the leading institutions. Prominent research themes identified are "endophyte," "green synthesis," "antimicrobial," "anti-cancer," and "biological activities," indicating a shift towards environmentally sustainable drug development. Our findings highlight the considerable potential of for developing new anticancer therapies and underscore the necessity for further research to harness these natural compounds for clinical use.
PubMed: 38812679
DOI: 10.3389/fmicb.2024.1379602 -
Anais Da Academia Brasileira de Ciencias 2024Sesbania virgata (Cav.) Pers. seeds are protein sources with health and environmental benefits. In this research, proteins with lectin activity were identified in a...
Sesbania virgata (Cav.) Pers. seeds are protein sources with health and environmental benefits. In this research, proteins with lectin activity were identified in a protein fraction from S. virgata seeds (PFLA), as well its antioxidant and antimicrobial potentials, in addition to cytotoxic effects. To obtain PFLA, seed flour was homogenized in Glycine-NaOH (100 mM; pH 9.0; NaCl 150 mM) and precipitated in ammonium sulfate. PFLA concentrates bioactive lectins (32 HU/mL, 480 HU/gFa, 18.862 HU/mgP) and essential amino acids (13.36 g/100g protein). PFLA exerts antioxidant activity, acting as a promising metal chelating agent (~77% of activity). Analyzes of cell culture assay results suggest that antioxidant activity of PFLA may be associated with the recruitment of essential molecules to prevent the metabolic impairment of cells exposed to oxidative stress. PFLA (256 - 512 µg/mL) also exhibits antifungal activity, inhibiting the growth of Aspergillus flavus, Candida albicans, Candida tropicalis and Penicillium citrinum. Cytotoxic analysis indicates a tendency of low interference in the proliferation of 3T3 and HepG2 cells in the range of PFLA concentrations with biological activity. These findings support the notion that PFLA is a promising adjuvant to be applied in current policies on the management of metal ion chelation and fungal infections.
Topics: Seeds; Antioxidants; Antifungal Agents; Sesbania; Humans; Plant Proteins; Microbial Sensitivity Tests; Animals; Mice; Plant Extracts; Hep G2 Cells
PubMed: 38808874
DOI: 10.1590/0001-3765202420230043 -
Therapeutic Advances in Rare Disease 2024A pulmonary nodule is a rare subtype of chronic pulmonary aspergillosis. The diagnosis is difficult and is histological. There are only a few reports on such cases....
A pulmonary nodule is a rare subtype of chronic pulmonary aspergillosis. The diagnosis is difficult and is histological. There are only a few reports on such cases. Here, we report five cases of pulmonary nodules confirmed by surgery and pathology in immunocompetent patient and review the literature. Among the five patients in this group, three were females and two were males, aged 44-73 years old. Two cases had hemoptysis onset, and three cases were found to have a slow disease course on chest CT during imaging, ranging from months to years. The white blood cell count, carcinoembryonic antigen, and blood Galactomannan (GM) tests in five cases were all within normal range. Four cases had normal blood C-reactive protein, and one case had an increase. On imaging, there were two cases in the upper lobe of the right lung, two cases in the lower lobe of the left lung, one case in the upper lobe of the left lung, three cases were solitary nodular shadows, and two cases were nodular shadows with cavity formation, including one case with calcification, four cases with bronchial dilation shadows, and one case with gas containing cavity shadows. Five cases were treated with surgical resection and confirmed by histopathological examination. All five patients did not receive antifungal treatment after surgery, and there was no recurrence of Aspergillus nodules during regular follow-up.
PubMed: 38808316
DOI: 10.1177/26330040241252446 -
Cureus Apr 2024Fosmanogepix, a prodrug of Manogepix (MGX), is a groundbreaking antifungal agent with broad-spectrum activity against yeasts, including and , as well as molds. It... (Review)
Review
Fosmanogepix, a prodrug of Manogepix (MGX), is a groundbreaking antifungal agent with broad-spectrum activity against yeasts, including and , as well as molds. It exhibits effectiveness against drug-resistant strains, such as strains resistant to and strains resistant to azoles. Furthermore, fosmanogepix shows activity against pathogens that typically resist other classes of drugs, such as , , and , although its efficacy against Mucorales varies. In animal models, fosmanogepix has demonstrated notable effectiveness against disseminated infections caused by various species, , and . It has also shown efficacy in pulmonary infection models involving , , , , and . Clinical trials have revealed excellent oral bioavailability (>90%), enabling a seamless transition between intravenous and oral formulations without compromising blood concentrations. Fosmanogepix exhibits favorable profiles in terms of drug interactions, tolerability, and extensive distribution in various tissues, making it an appealing choice for treating invasive fungal infections. This comprehensive review aims to examine the outcomes of published data on fosmanogepix, encompassing in vitro, in vivo, and clinical investigations.
PubMed: 38807795
DOI: 10.7759/cureus.59210 -
Biotechnology For Biofuels and... May 2024Aspergillus tubingensis is a citric acid-producing fungus that can utilize sugars in hydrolysate of lignocellulosic biomass such as sugarcane bagasse and, unlike A....
BACKGROUND
Aspergillus tubingensis is a citric acid-producing fungus that can utilize sugars in hydrolysate of lignocellulosic biomass such as sugarcane bagasse and, unlike A. niger, does not produce mycotoxins. To date, no attempt has been made to model its metabolism at genome scale.
RESULTS
Here, we utilized the whole-genome sequence (34.96 Mb length) and the measured biomass composition to reconstruct a genome-scale metabolic model (GSMM) of A. tubingensis DJU120 strain. The model, named iMK1652, consists of 1652 genes, 1657 metabolites and 2039 reactions distributed over four cellular compartments. The model has been extensively curated manually. This included removal of dead-end metabolites and generic reactions, addition of secondary metabolite pathways and several transporters. Several mycotoxin synthesis pathways were either absent or incomplete in the genome, providing a genomic basis for the non-toxinogenic nature of this species. The model was further refined based on the experimental phenotypic microarray (Biolog) data. The model closely captured DJU120 fermentative data on glucose, xylose, and phosphate consumption, as well as citric acid and biomass production, showing its applicability to capture citric acid fermentation of lignocellulosic biomass hydrolysate.
CONCLUSIONS
The model offers a framework to conduct metabolic systems biology investigations and can act as a scaffold for integrative modelling of A. tubingensis.
PubMed: 38807234
DOI: 10.1186/s13068-024-02506-4 -
Cellular and Molecular Life Sciences :... May 2024Aspergillus ochraceus is the traditional ochratoxin A (OTA)-producing fungus with density-dependent behaviors, which is known as quorum sensing (QS) that is mediated by...
Aspergillus ochraceus is the traditional ochratoxin A (OTA)-producing fungus with density-dependent behaviors, which is known as quorum sensing (QS) that is mediated by signaling molecules. Individual cells trend to adapt environmental changes in a "whole" flora through communications, allowing fungus to occupy an important ecological niche. Signals perception, transmission, and feedback are all rely on a signal network that constituted by membrane receptors and intracellular effectors. However, the interference of density information in signal transduction, which regulates most life activities of Aspergillus, have yet to be elucidated. Here we show that the G protein-coupled receptor (GPCR) to cAMP pathway is responsible for transmitting density information, and regulates the key point in life cycle of A. ochraceus. Firstly, the quorum sensing phenomenon of A. ochraceus is confirmed, and identified the density threshold is 10 spores/mL, which represents the low density that produces the most OTA in a series quorum density. Moreover, the GprC that classified as sugar sensor, and intracellular adenylate cyclase (AcyA)-cAMP-PKA pathway that in response to ligands glucose and HODEs are verified. Furthermore, GprC and AcyA regulate the primary metabolism as well as secondary metabolism, and further affects the growth of A. ochraceus during the entire life cycle. These studies highlight a crucial G protein signaling pathway for cell communication that is mediated by carbohydrate and oxylipins, and clarified a comprehensive effect of fungal development, which include the direct gene regulation and indirect substrate or energy supply. Our work revealed more signal molecules that mediated density information and connected effects on important adaptive behaviors of Aspergillus ochraceus, hoping to achieve comprehensive prevention and control of mycotoxin pollution from interrupting cell communication.
Topics: Quorum Sensing; Aspergillus ochraceus; Signal Transduction; Glucose; Cyclic AMP; Adenylyl Cyclases; Receptors, G-Protein-Coupled; Fungal Proteins; Ochratoxins
PubMed: 38806811
DOI: 10.1007/s00018-024-05160-z -
PloS One 2024In this investigation, we explore the harnessing of bamboo shoot residues (BSR) as a viable source for ruminant feed through fungal treatment, with the overarching...
In this investigation, we explore the harnessing of bamboo shoot residues (BSR) as a viable source for ruminant feed through fungal treatment, with the overarching objective of elevating feed quality and optimizing bamboo shoot utilization. The white-rot fungi (Wr.fungi), Aspergillus niger (A.niger), and its co-cultures (A.niger&Wr.fungi) were employed to ferment BSR. And the impact of different fermentation methods and culture time on the chemical composition (Crude protein Ash, neutral detergent fibre and acid detergent fibers), enzyme activity (Cellulase, Laccase, Filter paperase and Lignin peroxidase activities), and rumen digestibility in vitro were assessed. The findings reveal a nota ble 30.39% increase in crude protein in fermented BSR, accompanied by respective decreases of 13.02% and 17.31% in acid detergent fiber and neutral detergent fibre content. Enzyme activities experienced augmentation post-fermentation with A.niger&Wr.fungi. Specifically, the peak Cellulase, Laccase, and Lignin peroxidase activities for BSR with Wr.fungi treatment reached 748.4 U/g, 156.92 U/g, and 291.61 U/g, respectively, on the sixth day of fermentation. Concurrently, NH3-N concentration exhibited an upward trend with prolonged fermentation time. Total volatile fatty acids registered a decline, and the Acetate/Propionate ratio reached its nadir after 6 days of fermentation under the A.niger&Wr.fungi treatment. These outcomes furnish a theoretical foundation for the development of ruminant feeds treated via fungal co-culture.
Topics: Animals; Animal Feed; Fermentation; Ruminants; Aspergillus niger; Plant Shoots; Rumen; Fungi
PubMed: 38805421
DOI: 10.1371/journal.pone.0302185 -
Biotech (Basel (Switzerland)) May 2024The enzymatic hydrolysis of agricultural residues like wheat bran enables the valorization of otherwise unused carbon sources for biotechnological processes. The...
The enzymatic hydrolysis of agricultural residues like wheat bran enables the valorization of otherwise unused carbon sources for biotechnological processes. The co-culture of and with wheat bran particles as substrate produces an enzyme set consisting of xylanases, amylases, and cellulases that is suitable to degrade lignocellulosic biomass to sugar monomers (D-glucose, D-xylose, and L-arabinose). An integrated one-pot process for enzyme production followed by hydrolysis in stirred tank bioreactors resulted in hydrolysates with overall sugar concentrations of 32.3 g L and 24.4 g L at a 25 L and a 1000 L scale, respectively, within 86 h. Furthermore, the residual solid biomass consisting of fermented wheat bran with protein-rich fungal mycelium displays improved nutritional properties for usage as animal feed due to its increased content of sugars, protein, and fat.
PubMed: 38804297
DOI: 10.3390/biotech13020015 -
Infection and Drug Resistance 2024The role of -specific IgG antibody test in the diagnosis of non-neutropenic invasive pulmonary aspergillosis (IPA) is still uncertain, and related studies are also...
BACKGROUND
The role of -specific IgG antibody test in the diagnosis of non-neutropenic invasive pulmonary aspergillosis (IPA) is still uncertain, and related studies are also limited.
PURPOSE
This study aims to evaluate the quantitative test value of -specific IgG antibody in non-neutropenic IPA, which could provide additional evidence for related clinical diagnosis.
METHODS
This prospective study collected clinical data of suspected IPA patients from January, 2020 to December, 2022, and patients were divided into two groups, IPA and non-IPA. The study analyzed clinical characteristics and diagnostic value of -specific IgG antibody test, using the receiver operating characteristic (ROC) curve to evaluate diagnostic efficacy.
RESULTS
The study enrolled 59 IPA cases and 68 non-IPA cases, the average admission age of IPA group was 63.2±9.6 (33-79), and the gender ratio (male:female) of IPA group was 42:17. The proportion of patients with history of smoking and COPD were higher in IPA group (59.3% vs 39.7%, =0.027; 33.9% vs 14.7%, =0.011, respectively). The level of -specific IgG antibody in IPA group was significantly higher than non-IPA group (202.1±167.0 vs 62.6±58.0, <0.001). The area under the ROC curve was 0.799 (95%CI: 0.718, 0.865 <0.001), and the cut-off with best diagnostic efficacy was 91 AU/mL.
CONCLUSION
Immunological test plays an important role in the diagnosis of pulmonary aspergillosis, and -specific IgG antibody test has the good diagnostic value in non-neutropenic IPA.
PubMed: 38803521
DOI: 10.2147/IDR.S460513