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Journal of Agricultural and Food... Jun 2024This study reports a peptide design model for engineering fusion-expressed antimicrobial peptides (AMPs) with the AflR dinuclear zinc finger motif to improve the defense...
This study reports a peptide design model for engineering fusion-expressed antimicrobial peptides (AMPs) with the AflR dinuclear zinc finger motif to improve the defense against aflatoxins and . The study identified AflR, a ZnCys-type sequence-specific DNA-binding protein, as a key player in the regulation of aflatoxin biosynthesis. By integrating the AflR motif into AMPs, we demonstrate that these novel fusion peptides significantly lower the minimum inhibitory concentrations (MICs) and reduce aflatoxin B and B levels, outperforming traditional AMPs. Comprehensive analysis, including bioinformatics and structural determination, elucidates the enhanced structure-function relationship underlying their efficacy. Furthermore, the study reveals the possibility that the fusion peptides have the potential to bind to the DNA binding sites of transcriptional regulators, binding DNA sites of key transcriptional regulators, thereby inhibiting genes critical for aflatoxin production. This research not only deepens our understanding of aflatoxin inhibition mechanisms but also presents a promising avenue for developing advanced antifungal agents, which are essential for global food safety and crop protection.
Topics: Aspergillus flavus; Zinc Fingers; Antimicrobial Peptides; Aflatoxins; Protein Engineering; Microbial Sensitivity Tests; Antifungal Agents; Recombinant Fusion Proteins
PubMed: 38830379
DOI: 10.1021/acs.jafc.4c01259 -
Journal of Family Medicine and Primary... Apr 2024SARS-COV virus operates as a significant risk factor for invasive fungal aspergillosis and mucormycosis. Successful management of this fulminant infection requires early...
BACKGROUND
SARS-COV virus operates as a significant risk factor for invasive fungal aspergillosis and mucormycosis. Successful management of this fulminant infection requires early recognition of the disease and aggressive medical or surgical interventions to prevent the high morbidity and mortality associated with the disease process.
AIMS AND OBJECTIVE OF THE STUDY
1. To isolate and identify different species of fungi among acute rhinosinusitis patients. 2. To assess the association of risk factors causing fungal rhinosinusitis. 3. To assess the changing trend in fungal rhinosinusitis during the COVID era.
MATERIAL AND METHODS
This is a retrospective observational study conducted from May 2020 to October 2022, attending the ENT department and relevant data were collected from the medical records department of ABVIMS and Dr RML Hospital, New Delhi, a Tertiary Care Referral Centre in India. The major risk factors studied were age, gender, COVID-19 infection and underlying diseases (such as diabetes mellitus, ischaemic heart disease, hypertension, malignancies, chronic kidney DISEASES, etc.); details of corticosteroid use of all patients were recorded in the datasheet. The pandemic data was divided into three distinct time periods/waves/eras, i.e., first, second, and third waves, each of which included ten months, to examine the changing trend in fungal rhinosinusitis in the pandemic era of COVID-19.
RESULTS
A total of 412 patients out of which 236 patients were clinically diagnosed with fungal sinusitis based on revised EORTC criteria. The most common site involved was the orbit with paranasal sinus and eye 86/236 (36.4%), followed by involvement of nasal and paranasal sinus alone 68/236 (28.8%). The most prevalent age range affected was 40 to 50 years. The most commonly associated comorbidity was diabetes mellitus (DM) in 176 (74.5%), followed by head and neck malignancies in 22 (9.32%) patients. Thirty-eight (50.6%) species and 18 (24%) were the most common isolated fungal species on culture, followed by spp. 14 (18.6%) and 5 (6.6%) in the period. In the second wave of COVID, there was a surge in cases 36 (45%) and after the second wave, the cases increased by 14 (19%) during Jan-Oct 2022.
CONCLUSION
With the continuing coronavirus pandemic, there is an unprecedented and discernible rise in the prevalence of acute invasive fungal sinusitis certainly a spike in cases of Aspergillus infection was observed, probably due to unprecedented usage of Amphotericin B for the treatment of mucormycosis during the third wave This underlines the importance of the need to tailor our treatment protocol as per the etiological agents hence the right antifungal drugs combined with urgent surgical procedures on a case-to-case basis may certainly increase the chances of survival.
PubMed: 38827671
DOI: 10.4103/jfmpc.jfmpc_871_23 -
Applied Microbiology and Biotechnology May 2024Mycotoxin production by aflatoxin B1 (AFB1) -producing Aspergillus flavus Zt41 and sterigmatocystin (ST) -hyperproducer Aspergillus creber 2663 mold strains on corn and...
Mycotoxin production by aflatoxin B1 (AFB1) -producing Aspergillus flavus Zt41 and sterigmatocystin (ST) -hyperproducer Aspergillus creber 2663 mold strains on corn and rice starch, both of high purity and nearly identical amylose-amylopectin composition, as the only source of carbon, was studied. Scanning electron microscopy revealed average starch particle sizes of 4.54 ± 0.635 µm and 10.9 ± 2.78 µm, corresponding to surface area to volume ratios of 127 1/µm for rice starch and 0.49 1/µm for corn starch. Thus, a 2.5-fold difference in particle size correlated to a larger, 259-fold difference in surface area. To allow starch, a water-absorbing powder, to be used as a sole food source for Aspergillus strains, a special glass bead system was applied. AFB1 production of A. flavus Zt41 was determined to be 437.6 ± 128.4 ng/g and 90.0 ± 44.8 ng/g on rice and corn starch, respectively, while corresponding ST production levels by A. creber 2663 were 72.8 ± 10.0 µg/g and 26.8 ± 11.6 µg/g, indicating 3-fivefold higher mycotoxin levels on rice starch than on corn starch as sole carbon and energy sources. KEY POINTS: • A glass bead system ensuring the flow of air when studying powders was developed. • AFB1 and ST production of A. flavus and A. creber on rice and corn starches were studied. • 3-fivefold higher mycotoxin levels on rice starch than on corn starch were detected.
Topics: Oryza; Zea mays; Starch; Aspergillus; Aspergillus flavus; Aflatoxin B1; Sterigmatocystin; Microscopy, Electron, Scanning; Particle Size; Mycotoxins; Glass
PubMed: 38809353
DOI: 10.1007/s00253-024-13190-7 -
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 -
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 -
Saudi Pharmaceutical Journal : SPJ :... Jun 2024The menace of microbial resistance and re-emerging disease is still a problem for healthcare givers globally, and the need for newer sources of potent antibiotics has...
The menace of microbial resistance and re-emerging disease is still a problem for healthcare givers globally, and the need for newer sources of potent antibiotics has become paramount. This study investigated the antimicrobial and antiulcer activities of Streptomyces isolate SOM013. Streptomyces isolates were cultivated and purified following standard microbiological protocols. Secondary metabolites were recovered and characterized from Streptomyces isolate SOM013 via broth fermentation and extraction. Varying concentrations (0.5 mg/mL, 0.025 mg/mL and 0.0125 mg/mL) of the SOM013 extract were used for antimicrobial screening against resistant bacteria and medically important fungi (methicillin-resistant , Oxacillin resistant , , extended broad-spectrum resistant , and ). The antiulcer activity of the SOM013 was also examined in a methanol-induced gastric ulcer animal model. A total of 23 Streptomyces spp were recovered from the study. Methanolic extract of the SOM013 isolates was more potent across the clinical test microorganisms compared to water extract. The antimicrobial activity was dose dependent, with methanolic extract at 0.05 g/mL displaying the highest zone of inhibition (18.8 ± 0.3 mm) when tested against extended broad-spectrum resistant . Further, the extract's ulcer index and protection efficacy were significant as the concentration increased (P < 0.01). SOM013 isolate has a moderate antimicrobial and high antiulcer activity worthy of pharmacological exploration.
PubMed: 38799000
DOI: 10.1016/j.jsps.2024.102101 -
Scientific Reports May 2024Heavy metal accumulation is one of the major agronomic challenges that has seriously threatened food safety. As a result, metal-induced phytotoxicity concerns require...
Heavy metal accumulation is one of the major agronomic challenges that has seriously threatened food safety. As a result, metal-induced phytotoxicity concerns require quick and urgent action to retain and maintain the physiological activities of microorganisms, the nitrogen pool of soils, and the continuous yields of wheat in a constantly worsening environment. The current study was conducted to evaluate the plant growth-promoting endophytic Aspergillus flavus AUMC 16,068 and its EPS for improvement of plant growth, phytoremediation capacity, and physiological consequences on wheat plants (Triticum aestivum) under lead stress. After 60 days of planting, the heading stage of wheat plants, data on growth metrics, physiological properties, minerals content, and lead content in wheat root, shoot, and grains were recorded. Results evoked that lead pollution reduced wheat plants' physiological traits as well as growth at all lead stress concentrations; however, inoculation with lead tolerant endophytic A. flavus AUMC 16,068 and its respective EPS alleviated the detrimental impact of lead on the plants and promoted the growth and physiological characteristics of wheat in lead-contaminated conditions and also lowering oxidative stress through decreasing (CAT, POD, and MDA), in contrast to plants growing in the un-inoculated lead polluted dealings. In conclusion, endophytic A. flavus AUMC 16,068 spores and its EPS are regarded as eco-friendly, safe, and powerful inducers of wheat plants versus contamination with heavy metals, with a view of protecting plant, soil, and human health.
Topics: Triticum; Lead; Aspergillus flavus; Endophytes; Stress, Physiological; Polysaccharides; Biodegradation, Environmental; Soil Pollutants; Oxidative Stress; Plant Roots
PubMed: 38796501
DOI: 10.1038/s41598-024-61936-0 -
Journal of Applied Microbiology May 2024To develop antifungal lactic acid bacteria (LAB) and investigate their antifungal mechanisms against Aspergillus flavus in aflatoxin (AF) production.
AIMS
To develop antifungal lactic acid bacteria (LAB) and investigate their antifungal mechanisms against Aspergillus flavus in aflatoxin (AF) production.
METHODS AND RESULTS
We isolated 179 LABs from cereal-based fermentation starters and investigated their antifungal mechanism against A. flavus through liquid chromatography-mass spectrometry and co-culture analysis techniques. Of the 179 isolates, antifungal activity was identified in Pediococcus pentosaceus, Lactobacillus crustorum, and Weissella paramesenteroides. These LABs reduced AF concentration by (i) inhibiting mycelial growth, (ii) binding AF to the cell wall, and (iii) producing antifungal compounds. Species-specific activities were also observed, with P. pentosaceus inhibiting AF production and W. paramesenteroides showing AF B1 binding activity. In addition, crucial extracellular metabolites for selecting antifungal LAB were involved in the 2',3'-cAMP-adenosine and nucleoside pathways.
CONCLUSIONS
This study demonstrates that P. pentosaceus, L. crustorum, and W. paramesenteroides are key LAB strains with distinct antifungal mechanisms against A. flavus, suggesting their potential as biological agents to reduce AF in food materials.
Topics: Aspergillus flavus; Coculture Techniques; Antifungal Agents; Metabolomics; Lactobacillales; Fermentation; Aflatoxins; Edible Grain; Pediococcus pentosaceus; Antibiosis; Food Microbiology
PubMed: 38794887
DOI: 10.1093/jambio/lxae112 -
Pharmaceuticals (Basel, Switzerland) May 2024Recently, there has been a surge towards searching for primitive treatment strategies to discover novel therapeutic approaches against multi-drug-resistant pathogens....
Recently, there has been a surge towards searching for primitive treatment strategies to discover novel therapeutic approaches against multi-drug-resistant pathogens. Endophytes are considered unexplored yet perpetual sources of several secondary metabolites with therapeutic significance. This study aims to isolate and identify the endophytic fungi from L. fruit peels using morphological, microscopical, and transcribed spacer (ITS-rDNA) sequence analysis; extract the fungus's secondary metabolites by ethyl acetate; investigate the chemical profile using UPLC/MS; and evaluate the potential antibacterial, antibiofilm, and antiviral activities. An endophytic fungus was isolated and identified as L. from the fruit peels. The UPLC/MS revealed seven compounds with various chemical classes. The antimicrobial activity of the fungal ethyl acetate extract (FEA) was investigated against different Gram-positive and Gram-negative standard strains, in addition to resistant clinical isolates using the agar diffusion method. The CPE-inhibition assay was used to identify the potential antiviral activity of the crude fungal extract against low pathogenic human coronavirus (HCoV 229E). Selective Gram-positive antibacterial and antibiofilm activities were evident, demonstrating pronounced efficacy against both methicillin-resistant (MRSA) and methicillin-sensitive (MSSA). However, the extract exhibited very weak activity against Gram-negative bacterial strains. The ethyl acetate extract of L exhibited an interesting antiviral activity with a half maximal inhibitory concentration (IC) value of 27.2 µg/mL against HCoV 229E. Furthermore, in silico virtual molecular docking-coupled dynamics simulation highlighted the promising affinity of the identified metabolite, orienting towards three MRSA biotargets and HCoV 229E main protease as compared to reported reference inhibitors/substrates. Finally, ADME analysis was conducted to evaluate the potential oral bioavailability of the identified metabolites.
PubMed: 38794226
DOI: 10.3390/ph17050656 -
International Journal of Molecular... May 2024The current review aims to outline and summarize the latest research on aflatoxin, with research studies describing natural, herbal and chemical compound applications in... (Review)
Review
AIMS
The current review aims to outline and summarize the latest research on aflatoxin, with research studies describing natural, herbal and chemical compound applications in animal (pig) models and in vitro cellular studies. Aflatoxin, a carcinogenic toxin metabolite, is produced by in humid environments, posing a threat to human health and crop production. The current treatment involves the prevention of exposure to aflatoxin and counteracting its harmful toxic effects, enabling survival and research studies on an antidote for aflatoxin.
OBJECTIVES
To summarize current research prospects and to outline the influence of aflatoxin on animal forage in farm production, food and crop processing. The research application of remedies to treat aflatoxin is undergoing development to pinpoint biochemical pathways responsible for aflatoxin effects transmission and actions of treatment.
SIGNIFICANCE
To underline the environmental stress of aflatoxin on meat and dairy products; to describe clinical syndromes associated with aflatoxicosis on human health that are counteracted with proposed treatment and preventive interventions. To understand how to improve the health of farm animals with feed conditions.
Topics: Animals; Animal Feed; Humans; Aflatoxin B1; Food Contamination; Aspergillus flavus
PubMed: 38791343
DOI: 10.3390/ijms25105305