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Equisetin was isolated from endophytic fungus Fusarium sp. JDJR1 via bioassay-guided isolation, and it was evaluated as an anti-microbial and herbicidal agent. Bioactivity assessments revealed that equisetin exhibited a broad spectrum of fungicidal and anti-bacterial activity against various plant pathogens. The EC50 values against Botrytis cinerea, Fusarium graminearum, Sclerotinia sclerotiorum, and Rhizoctonia solani ranged from 10.7 to 21.0 μg/mL. Notably, equisetin demonstrated activity against Xanthomonas oryzae pv. oryzicola, Xanthomonas oryzae pv. oryzae and Pseudomonas solanacearum with an MIC range of 4–16 μg/mL, surpassing the efficacy of the positive control: streptomycin sulfate. Equisetin, at a concentration of 100 μg/mL, could completely inhibit the spore germination of F. graminearum. In in vivo protection experiments, the protective efficacy of equisetin against B. cinerea on tomato fruits at 200 μg/mL reached 72.9%. Furthermore, in herbicidal activity tests that use the Petri dish bioassay method, equisetin had a good inhibitory effect on the root growth of weeds. At a concentration of 100 μg/mL, the inhibition rates for Echinochloa crusgalli and Eclipta prostrata root were 98.8 and 94.4%, respectively. [ABSTRACT FROM AUTHOR]

Mammalian cells act as reservoirs of internalized bacteria to circumvent extracellular antibacterial compounds, resulting in relapse and reinfection diseases. The intracellular persistence of Staphylococcus aureus renders most traditional antibiotics useless, due to their inadequate subcellular accumulation. To replenish our antibiotic arsenal, we found that a marine-derived compound, equisetin, efficiently eliminates intracellular S. aureus by potentiating the host autophagy and inducing mitochondrial-mediated ROS generation to clear the invading S. aureus. The remarkable anti-infection activity of equisetin was validated in a peritonitis-infected mouse model. The marine product equisetin utilizes a unique dual mechanism to modulate the host–pathogen interaction in the clearance of intracellular bacteria. Thus, equisetin is an inspiring host-acting candidate for overcoming intracellular pathogens. [ABSTRACT FROM AUTHOR]

This study was conducted to elucidate evolutionary relationships and species diversity within the Fusarium buharicum species complex (FBSC). We also evaluate the potential of these species to produce mycotoxins and other bioactive secondary metabolites. Maximum likelihood and maximum parsimony analyses of sequences from portions of four marker loci (ITS rDNA, TEF1, RPB1, and RPB2) and the combined 4495 bp data set support recognition of seven genealogically exclusive species within the FBSC. Two of the three newly discovered species are formally described as F. abutilonis and F. guadeloupense based on concordance of gene genealogies and morphological data. Fusarium abutilonis induces leaf, stem, and root lesions on several weedy Malvaceae (Abution theophrasti, Anoda cristata, Sida spinosa) and a fabaceous host (Senna obtusifolia) in North America and also was recovered from soil in New Caledonia. Fusarium abutilonis, together with its unnamed sister, Fusarium sp. ex common marsh mallow (Hibiscus moscheutos) from Washington state, and F. buharicum pathogenic to cotton and kenaf in Russia and Iran, respectively, were strongly supported as a clade of malvaceous pathogens. The four other species of the FBSC are not known to be phytopathogenic; however, F. guadeloupense was isolated from human blood in Texas and soil in Guadeloupe. The former isolate is unique because it represents the only known case of a fusarial infection disseminated hematogenously by a species lacking microconidia and the only documented fusariosis caused by a member of the FBSC. Whole genome sequence data and extracts of cracked maize kernel cultures were analyzed to assess the potential of FBSC isolates to produce mycotoxins, pigments, and phytohormones. [ABSTRACT FROM AUTHOR]

The Beibu Gulf harbors abundant underexplored marine microbial resources, which are rich in diversified secondary metabolites. The genera Vibrio is a well-known pathogenic bacterium of aquatic animals. In this study, 22 fungal strains were isolated and identified from the Beibu Gulf coral via the serial dilution method and internal transcribed spacer (ITS) sequence analysis, which were further divided into three branches by phylogenetic tree analysis. The crude extracts of them via small-scale fermentation were selected for the screening of inhibitory activity against Vibrio alginalyticus , Vibrio coralliilyticus , Vibrio harveyi , Vibrio parahaemolyticus , Vibrio owensii , and Vibrio shilonii. The results showed that eight fungal extracts displayed anti- Vibrio activity via the filter paper disk assay. Several of them showed strong inhibitory effects. Then, two tetramic acid alkaloids, equisetin (1) and 5′-epiequisetin (2), were identified from Fusarium equiseti BBG10 by bioassay-guided isolation, both of which inhibited the growth of Vibrio spp. with the MIC values of 86–132 μg/ml. The scanning electron microscope results showed that cell membranes of Vibrio became corrugated, distorted or ruptured after treatment with 1 and 2. Taken together, this study provided eight fungal isolates with anti- Vibrio potentials, and two alkaloid-type antibiotics were found with anti- Vibrio effects from the bioactive strain F. equiseti BBG10. Our findings highlight the importance of exploring promising microbes from the Beibu Gulf for the identification of anti- Vibrio for future antibiotic development. [ABSTRACT FROM AUTHOR]

The Beibu Gulf harbors abundant underexplored marine microbial resources, which are rich in diversified secondary metabolites. The genera Vibrio is a well-known pathogenic bacterium of aquatic animals. In this study, 22 fungal strains were isolated and identified from the Beibu Gulf coral via the serial dilution method and internal transcribed spacer (ITS) sequence analysis, which were further divided into three branches by phylogenetic tree analysis. The crude extracts of them via small-scale fermentation were selected for the screening of inhibitory activity against Vibrio alginalyticus, Vibrio coralliilyticus, Vibrio harveyi, Vibrio parahaemolyticus, Vibrio owensii, and Vibrio shilonii. The results showed that eight fungal extracts displayed anti-Vibrio activity via the filter paper disk assay. Several of them showed strong inhibitory effects. Then, two tetramic acid alkaloids, equisetin (1) and 5′-epiequisetin (2), were identified from Fusarium equiseti BBG10 by bioassay-guided isolation, both of which inhibited the growth of Vibrio spp. with the MIC values of 86–132 μg/ml. The scanning electron microscope results showed that cell membranes of Vibrio became corrugated, distorted or ruptured after treatment with 1 and 2. Taken together, this study provided eight fungal isolates with anti-Vibrio potentials, and two alkaloid-type antibiotics were found with anti-Vibrio effects from the bioactive strain F. equiseti BBG10. Our findings highlight the importance of exploring promising microbes from the Beibu Gulf for the identification of anti-Vibrio for future antibiotic development.

Mammalian cells act as reservoirs of internalized bacteria to circumvent extracellular antibacterial compounds, resulting in relapse and reinfection diseases. The intracellular persistence of Staphylococcus aureus renders most traditional antibiotics useless, due to their inadequate subcellular accumulation. To replenish our antibiotic arsenal, we found that a marine-derived compound, equisetin, efficiently eliminates intracellular S. aureus by potentiating the host autophagy and inducing mitochondrial-mediated ROS generation to clear the invading S. aureus. The remarkable anti-infection activity of equisetin was validated in a peritonitis-infected mouse model. The marine product equisetin utilizes a unique dual mechanism to modulate the host–pathogen interaction in the clearance of intracellular bacteria. Thus, equisetin is an inspiring host-acting candidate for overcoming intracellular pathogens.

The overuse of antibiotics and the scarcity of new drugs have led to a serious antimicrobial resistance crisis, especially for multi-drug resistant (MDR) Gram-negative bacteria. In the present study, we investigated the antimicrobial activity of a marine antibiotic equisetin in combination with colistin against Gram-negative bacteria and explored the mechanisms of synergistic activity. We tested the synergistic effect of equisetin in combination with colistin on 23 clinical mcr-1 positive isolates and found that 4 µg/mL equisetin combined with 1 µg/mL colistin showed 100% inhibition. Consistently, equisetin restored the sensitivity of 10 species of mcr-1 positive Gram-negative bacteria to colistin. The combination of equisetin and colistin quickly killed 99.9% bacteria in one hour in time-kill assays. We found that colistin promoted intracellular accumulation of equisetin in colistin-resistant E. coli based on LC-MS/MS analysis. Interestingly, equisetin boosted ROS accumulation in E. coli in the presence of colistin. Moreover, we found that equisetin and colistin lost the synergistic effect in two LPS-deficient A. baumannii strains. These findings suggest that colistin destroys the hydrophobic barrier of Gram-negative bacteria, facilitating equisetin to enter the cell and exert its antibacterial effect. Lastly, equisetin restored the activity of colistin in a G. mellonella larvae infection model. Collectively, these results reveal that equisetin can potentiate colistin activity against MDR Gram-negative bacteria including colistin-resistant strains, providing an alternative approach to address Gram-negative pathogens associated with infections in clinics.

[Display omitted] • Binding Mechanism: The docking studies indicate that Equisetin forms hydrogen bonds with specific amino acid residues of HSA, contributing to the complex's structural stability. • Binding Site: Equisetin binds at site III (domains IB) of HAS, this binding site is predominantly within a hydrophobic cavity, leading to the encapsulation of Equisetin by HSA. • Conformational Change: The interaction of Equisetin with HSA induces minor unfolding of the protein polypeptide and significant alterations in the secondary structure of HSA. This results in a conformational change that exposes previously concealed hydrophobic regions. Equisetin, a bioactive compound of marine origin, offers compelling inhibitory properties against HIV-1 transcriptase. To gain comprehensive insights into the interaction of Equisetin with human serum albumin (HSA), we utilized a multipronged approach involving spectroscopy, isothermal titration calorimetry (ITC) and molecular docking. Our fluorescence analyses confirmed that the interaction between Equisetin and HSA results in a significant quenching of HSA's fluorescence, primarily achieved through a dynamic mechanism aided by hydrogen bonding and van der Waals forces. Isothermal titration calorimetry (ITC) measurements revealed an impressive binding affinity of Equisetin for HSA, quantified to be 4.3 × 107 mol L−1. Molecular docking studies illustrated that Equisetin binds at site III of HSA, with specific amino acid residues, GLN-104 and LYS-106, playing a pivotal role. Further, our study discovered that the interaction induces slight unfolding of HSA's polypeptide chain and significant alterations in its secondary structure, thereby triggering the exposure of previously concealed hydrophobic regions. This comprehensive study enhances our understanding of Equisetin's interaction with serum proteins, potentially influencing its pharmacokinetics and pharmacodynamics, and opening avenues for future research and therapeutic applications. [ABSTRACT FROM AUTHOR]

Methicillin-resistant Staphylococcus aureus (MRSA) is emerging as a serious pathogenic bacterium in the clinical setting, and antibiotic resistance is spreading faster than the introduction of new agents to kill such bacteria. In our study, Fusarium sp. 152, a marine fungus obtained from the South China Sea, was fermented to screen new anti-MRSA compounds including equisetin (EQ) with a MIC value of 1 µg/mL. Then, EQ was loaded into nanoparticle-based polyvinylpyrrolidone (PVP) electrospinning to facilitate its practical use. After electrospinning, the EQ nanofibers (EQ/NPs nanofiber) were 374.9 nm in diameter, and they showed a good flexibility and foldability. Additionally, the EQ/NPs nanofibers showed a better antibacterial effect both in vitro and in vivo than cefoxitin. Simultaneously, the infectious wounds treated with EQ/NPs nanofiber healed better and faster than those treated with EQ and cefoxitin. These findings strongly demonstrate that PVP-based electrospinning dressings are a candidate delivery carrier for the new anti-MRSA compound EQ for topical therapy. [ABSTRACT FROM AUTHOR]

Objective: To screen for the quorum-sensing (QS) inhibitors from marine-derived fungi and evaluate their anti-QS properties in Pseudomonas aeruginosa.Results: QS inhibitory activity was found in secondary metabolites of a marine fungus Fusarium sp. Z10 using P. aeruginosa QSIS-lasI biosensor. The major active compound of this fungus was isolated by HPLC and identified as equisetin. Subinhibitory concentration of equisetin could inhibit the formation of biofilm, swarming motility, and the production of virulence factors in P. aeruginosa. The inhibition of las, PQS, and rhl system by equisetin were determined using Escherichia coli MG4/pKDT17, E.coli pEAL08-2, and E.coli pDSY, respectively. Real-time RT-PCR assays showed that equisetin could downregulate the mRNA expression of QS-related genes.Conclusions: Equisetin proved its potential as an inhibitor against P. aeruginosa QS system and might also serve as precursor compound in development of novel therapeutics for infectious diseases by optimal design of structures. [ABSTRACT FROM AUTHOR]

Background and aims: A study was performed to investigate the role of fungal metabolites released into the rhizosphere of replanted orchards as a potential biotic component of tree growth decline. Methods: The phytotoxicity of the gamma ray-sterilized crude culture filtrates of sixteen fungal species originating from replanted apple orchards was tested in a bioassay. Low molecular weight compounds released by Fusarium spp. were analyzed. Results: The fungal culture filtrates affected seedling growth and health with an activity that varied from growth inhibition to promotion. Three out of the six species of Fusarium tested produced species-specific mycotoxins such as equisetin and enniatin B and D (<1 μg ml and <6 μg ml, respectively) associated with root-tip necrosis, whereas fusaric acid (80-230 μg ml) was associated with asymptomatic plant growth inhibition. These findings were consistent with those obtained using pure compounds. Moreover, methoxyconidiol, paecilaminol, integrastatin B and other biologically active compounds, whose fungal origin and phytotoxicity have not yet been reported, were found. in all fungal filtrates. Conclusions: Findings suggest that i) phytopathogenicity of soil borne fungi can be expressed regardless of root infection; ii) a synergistic interaction between co-occurring mycotoxins and other biologically active compounds may explain plant growth inhibition. Iii) fungal metabolites released into soil may represent an underestimated component of nonspecific replant disease. [ABSTRACT FROM AUTHOR]

Background: Opuntia dillenii is an invasive plant well established in the harsh South-Eastern arid zone of Sri Lanka. Evidence suggests it is likely that the endophytic fungal populations of O. dillenii assist the host in overcoming biotic and abiotic stress by producing biologically active metabolites. With this in mind there is potential to discover novel natural products with useful biological activities from this hitherto poorly investigated source. Consequently, an investigation of the antimicrobial activities of the endophytes of O. dillenii, that occupies a unique ecological niche, may well provide useful leads in the discovery of new pharmaceuticals. Methods: Endophytic fungi were isolated from the surface sterilized cladodes and flowers of O. dillenii using several nutrient media and the antimicrobial activities were evaluated against three Gram-positive and two Gram-negative bacteria and Candida albicans. The two most bioactive fungi were identified by colony morphology and DNA sequencing. The secondary metabolite of the endophyte Fusarium sp. exhibiting the best activity was isolated via bioassay guided chromatography. The chemical structure was elucidated from the ESIMS and NMR spectroscopic data obtained for the active metabolite. The minimum inhibitory concentrations (MICs) of the active compound were determined. Results: Eight endophytic fungi were isolated from O. dillenii and all except one showed antibacterial activities against at least one of the test bacteria. All extracts were inactive against C. albicans. The most bioactive fungus was identified as Fusarium sp. and the second most active as Aspergillus niger. The structure of the major antibacterial compound of the Fusarium sp. was shown to be the tetramic acid derivative, equisetin. The MICs for equisetin were 8 µg mLT1 against Bacillus subtilis, 16 µg mL-1 against Staphylococcus aureus and Methicillin Resistant Staphylococcus aureus (MRSA). Conclusions: O. dillenii, harbors several endophytic fungi capable of producing antimicrobial substances with selective antibacterial properties. By producing biologically active secondary metabolites, such as equisetin isolated from the endophytic Fusarium sp., the endophytic fungal population may be assisting the host to successfully withstand stressful environmental conditions. Further investigations on the secondary metabolites produced by these endophytes may provide additional drug leads. [ABSTRACT FROM AUTHOR]

(+)-Fusarisetin A belongs to a group of acyl tetramic acid natural products that show potential anticancer activity. Equisetin, a biogenetically related acyl tetramic acid, contains the basic skeleton of (+)-fusarisetin A. We proposed that equisetin and (+)-fusarisetin A share a biosynthetic pathway that starts with naturally occurring ( S)-serine and an unsaturated fatty acid. In support of this hypothesis, we have demonstrated that a cyclization sequence involving an intramolecular Diels-Alder reaction followed by a Dieckmann cyclization of polyenoylamino acid yielded equisetin. The aerobic oxidation of equisetin, promoted by either MnIII/O2 or a reactive oxygen species (ROS) produced by visible-light chemistry, gave peroxyfusarisetin, which could be easily reduced to (+)-fusarisetin A. We report herein detailed information on the biogenetic synthesis of equisetin and (+)-fusarisetin A. [ABSTRACT FROM AUTHOR]

The overuse of antibiotics and the scarcity of new drugs have led to a serious antimicrobial resistance crisis, especially for multi-drug resistant (MDR) Gram-negative bacteria. In the present study, we investigated the antimicrobial activity of a marine antibiotic equisetin in combination with colistin against Gram-negative bacteria and explored the mechanisms of synergistic activity. We tested the synergistic effect of equisetin in combination with colistin on 23 clinical mcr-1 positive isolates and found that 4 µg/mL equisetin combined with 1 µg/mL colistin showed 100% inhibition. Consistently, equisetin restored the sensitivity of 10 species of mcr-1 positive Gram-negative bacteria to colistin. The combination of equisetin and colistin quickly killed 99.9% bacteria in one hour in time-kill assays. We found that colistin promoted intracellular accumulation of equisetin in colistin-resistant E. coli based on LC-MS/MS analysis. Interestingly, equisetin boosted ROS accumulation in E. coli in the presence of colistin. Moreover, we found that equisetin and colistin lost the synergistic effect in two LPS-deficient A. baumannii strains. These findings suggest that colistin destroys the hydrophobic barrier of Gram-negative bacteria, facilitating equisetin to enter the cell and exert its antibacterial effect. Lastly, equisetin restored the activity of colistin in a G. mellonella larvae infection model. Collectively, these results reveal that equisetin can potentiate colistin activity against MDR Gram-negative bacteria including colistin-resistant strains, providing an alternative approach to address Gram-negative pathogens associated with infections in clinics. [ABSTRACT FROM AUTHOR]

Antibiotic resistance nowadays is spreading much faster than the introduction of new antibiotics into clinical practice. There is an urgent need for potential compounds to combat multidrug-resistant (MDR) bacteria. Marine fungi provide a promising source for chemical diversity with antibiotic-like molecules. To identify structurally distinct compounds that effectively eradicate MDR pathogens and to control the development of antibiotic resistance, we have reinvestigated equisetin, a previously reported meroterpenoid isolated from a marine sponge-derived fungus. Equisetin exerted efficient antibacterial activities against either MRSA or VRE without detectable high-level resistance. Meanwhile, equisetin, as an antibiotic adjuvant, restores colistin susceptibility to colistin-resistant bacteria toward diverse Gram-negative pathogens. Intriguingly, the low-level equisetin-resistant Staphylococcus aureus displayed collateral sensitivity to multiple classes of existing antibiotics with decreased capacity to produce biofilm. Lastly, equisetin showed efficacy with MRSA in three infected animal models. This work suggests that equisetin derived from marine natural products is a promising lead to overcome antibiotic resistance, providing new insight in future antibiotic discovery and development.