Endophyte mediated biocontrol mechanisms of phytopathogens in agriculture.

The global human population is growing and demand for food is increasing. Global agriculture faces numerous challenges, including excessive application of synthetic pesticides, emergence of herbicide-and pesticide-resistant pathogenic microbes, and more frequent natural disasters associated with global warming. Searches for valuable endophytes have increased, with the aim of making agriculture more sustainable and environmentally friendly. Endophytic microbes are known to have a variety of beneficial effects on plants. They can effectively transfer nutrients from the soil into plants, promote plant growth and development, increase disease resistance, increase stress tolerance, prevent herbivore feeding, reduce the virulence of pathogens, and inhibit the growth of rival plant species. Endophytic microbes can considerably minimize the need for agrochemicals, such as fertilizers, fungicides, bactericides, insecticides, and herbicides in the cultivation of crop plants. This review summarizes current knowledge on the roles of endophytes focusing on their mechanisms of disease control against phytopathogens through the secretion of antimicrobial substances and volatile organic compounds, and the induction of systemic resistance in plants. Additionally, the beneficial roles of these endophytes and their metabolites in the control of postharvest diseases in plants have been summarized.

Biologically inspired nanoformulations for the control of bacterial canker pathogens Clavibacter michiganensis subsp. michiganensis and subsp. capsici.

Clavibacter michiganensis subsp. michiganensis (Cmm) and C. michiganensis subsp. capsici (Cmc) are phytopathogenic bacteria that cause bacterial canker disease in tomatoes and peppers, respectively. Bacterial canker disease poses serious challenges to solanaceous crops, causing significant yield losses and economic costs. Effective management necessitates the development of sustainable control strategies employing nanobiotechnology. In this study, the antibacterial effects of four Aspergillus sojae-mediated nanoformulations, including cobalt oxide nanoparticles (Co3O4 NPs), zinc oxide nanoparticles (ZnO NPs), cobalt ferrite nanoparticles (CoFe2O4 NPs), and CoFe2O4/functionalized multi-walled carbon nanotube (fMWCNT) bionanocomposite, were evaluated against Cmm and Cmc. The diameters of the zone of inhibition of A. sojae-mediated Co3O4 NPs, ZnO NPs, CoFe2O4 NPs, and CoFe2O4/fMWCNT bionanocomposite against Cmm and Cmc were 23.60mm, 22.09mm, 27.65mm, 22.51mm, and 19.33mm, 17.66mm, 21.64mm, 18.77mm, respectively. The broth microdilution assay was conducted to determine the minimal inhibitory and bactericidal concentrations. The MICs of Co3O4 NPs, ZnO NPs, CoFe2O4 NPs, and CoFe2O4/fMWCNT bionanocomposite against Cmm were 2.50mg/mL, 1.25mg/mL, 2.50mg/mL, and 2.50mg/mL, respectively. While, their respective MBCs against Cmm were 5.00mg/mL, 2.50mg/mL, 5.00mg/mL, and 5.00mg/mL. The respective MICs of Co3O4 NPs, ZnO NPs, CoFe2O4 NPs, and CoFe2O4/fMWCNT bionanocomposite against Cmc were 2.50mg/mL, 1.25mg/mL, 5.00mg/mL, and 5.00mg/mL. While, their respective MBCs against Cmc were 5.00mg/mL, 2.50mg/mL, 10.00mg/mL, and 10.00mg/mL. The morphological and ultrastructural changes of Cmm and Cmc cells were observed using field-emission scanning and transmission electron microscopy before and after treatment with sub-minimal inhibitory concentrations of the nanoformulations. Nanoformulation-treated bacterial cells became deformed and disrupted, displaying pits, deep cavities, and groove-like structures. The cell membrane detached from the bacterial cell wall, electron-dense particles accumulated in the cytoplasm, cellular components disintegrated, and the cells were lysed. Direct physical interactions between the prepared nanoformulations with Cmm and Cmc cells might be the major mechanism for their antibacterial potency. Further research is required for the in vivo application of the mycosynthesized nanoformulations as countermeasures to combat bacterial phytopathogens.

Characterization of Plant-Derived Natural Inhibitors of Dipeptidyl Peptidase-4 as Potential Antidiabetic Agents: A Computational Study.

Diabetes, characterized by elevated blood sugar levels, poses significant health and economic risks, correlating with complications like cardiovascular disease, kidney failure, and blindness. Dipeptidyl peptidase-4 (DPP-4), also referred to as T-cell activation antigen CD26 (EC 3.4.14.5.), plays a crucial role in glucose metabolism and immune function. Inhibiting DPP-4 was anticipated as a potential new therapy for diabetes. Therefore, identification of plant-based natural inhibitors of DPP-4 would help in eradicating diabetes worldwide. Here, for the identification of the potential natural inhibitors of DPP-4, we developed a phytochemicals library consisting of over 6000 phytochemicals detected in 81 medicinal plants that exhibited anti-diabetic potency. The library has been docked against the target proteins, where isorhamnetin, Benzyl 5-Amino-5-deoxy-2,3-O-isopropyl-alpha-D-mannofuranoside (DTXSID90724586), and 5-Oxo-7-[4-(trifluoromethyl) phenyl]-4H,6H,7H-[1,2]thiazolo[4,5-b]pyridine 3-carboxylic acid (CHEMBL3446108) showed binding affinities of -8.5, -8.3, and -8.3 kcal/mol, respectively. These compounds exhibiting strong interactions with DPP-4 active sites (Glu205, Glu206, Tyr547, Trp629, Ser630, Tyr662, His740) were identified. ADME/T and bioactivity predictions affirmed their pharmacological safety. Density functional theory calculations assessed stability and reactivity, while molecular dynamics simulations demonstrated persistent stability. Analyzing parameters like RMSD, RG, RMSF, SASA, H-bonds, MM-PBSA, and FEL confirmed stable protein-ligand compound formation. Principal component analysis provided structural variation insights. Our findings suggest that those compounds might be possible candidates for developing novel inhibitors targeting DPP-4 for treating diabetes.

Detection of Antagonistic Compounds Synthesized by Bacillus velezensis against Xanthomonas citri subsp. citri by Metabolome and RNA Sequencing.

Biological control of plant diseases has gained attraction for controlling various bacterial diseases at a field trial stage. An isolated endophytic bacterium, Bacillus velezensis 25 (Bv-25), from Citrus species had strong antagonistic activity against Xanthomonas citri subsp. citri (Xcc), which causes citrus canker disease. When Bv-25 was incubated in Landy broth or yeast nutrient broth (YNB), the ethyl acetate extract of Landy broth exhibited higher levels of antagonistic activity against Xcc compared to that of YNB. Therefore, the antimicrobial compounds in the two ethyl acetate extracts were detected by high performance liquid chromatography-mass spectrometry. This comparison revealed an increase in production of several antimicrobial compounds, including difficidin, surfactin, fengycin, and Iturin-A or bacillomycin-D by incubation in Landy broth. RNA sequencing for the Bv-25 grown in Landy broth were performed, and the differential expressions were detected for the genes encoding the enzymes for the synthesis of antimicrobial compounds, such as bacilysin, plipastatin or fengycin, surfactin, and mycosubtilin. Combination of metabolomics analysis and RNA sequencing strongly suggests that several antagonistic compounds, especially bacilysin produced by B. velezensis, exhibit an antagonistic effect against Xcc.

Identification of medicinal plant-based phytochemicals as a potential inhibitor for SARS-CoV-2 main protease (Mpro) using molecular docking and deep learning methods.

Highly transmissive and rapidly evolving Coronavirus disease-2019 (COVID-19), a viral disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), triggered a global pandemic, which is one of the most researched viruses in the academia. Effective drugs to treat people with COVID-19 have yet to be developed to reduce mortality and transmission. Studies on the SARS-CoV-2 virus identified that its main protease (Mpro) might be a potential therapeutic target for drug development, as this enzyme plays a key role in viral replication. In search of potential inhibitors of Mpro, we developed a phytochemical library consisting of 2431 phytochemicals from 104 Korean medicinal plants that exhibited medicinal and antioxidant properties. The library was screened by molecular docking, followed by revalidation by re-screening with a deep learning method. Recurrent Neural Networks (RNN) computing system was used to develop an inhibitory predictive model using SARS coronavirus Mpro dataset. It was deployed to screen the top 12 compounds based on their docked binding affinity that ranged from -8.0 to -8.9 kcal/mol. The top two lead compounds, Catechin gallate and Quercetin 3-O-malonylglucoside, were selected depending on inhibitory potency against Mpro. Interactions with the target protein active sites, including His41, Met49, Cys145, Met165, and Thr190 were also examined. Molecular dynamics simulation was performed to analyze root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (RG), solvent accessible surface area (SASA), and number of hydrogen bonds. Results confirmed the inflexible nature of the docked complexes. Absorption, distribution, metabolism, excretion, and toxicity (ADMET), as well as bioactivity prediction confirmed the pharmaceutical activities of the lead compound. Findings of this research might help scientists to optimize compatible drugs for the treatment of COVID-19 patients.

Biosynthesis, Molecular Regulation, and Application of Bacilysin Produced by Bacillus Species.

Microbes produce a diverse range of secondary metabolites in response to various environmental factors and interspecies competition. This enables them to become superior in a particular environment. Bacilysin, a dipeptide antibiotic produced by Bacillus species, is active against a broad range of microorganisms. Because of its simple structure and excellent mode of action, i.e., through the inhibition of glucosamine 6-phosphate synthase, it has drawn the attention of researchers. In addition, it acts as a pleiotropic signaling molecule that affects different cellular activities. However, all Bacillus species are not capable of producing bacilysin. The biosynthesis of bacilysin by Bacillus species is not uniform throughout the population; specificity and heterogeneity at both the strain and species levels has been observed. This review discusses how bacilysin is biosynthesized by Bacillus species, the regulators of its biosynthesis, its importance in the host, and the abiotic factors affecting bacilysin production.

Biocontrol of citrus bacterial canker caused by Xanthomonas citri subsp. citri by Bacillus velezensis.

Microorganisms with biocontrol capabilities against plant pathogens are considered as one of the most promising approaches for healthy crop management. In this study, ethyl acetate extracts of 25 Bacillus strains were investigated for their antagonistic effect on Xanthomonas citri subsp. citri (Xcc), which causes the citrus bacterial canker (CBC) disease. Among them, 21 strains exerted antibacterial activity against wild-type Xcc strains. Based on the strength of the antibacterial activity, nine Bacillus strains were selected for 16S rRNA analysis. 16S rRNA sequence homology revealed that several strains were closely related to B. velezensis, where strains with no antibacterial activity grouped as the soil-associated community of B. amyloliquefaciens. B. velezensis Bv-21 exhibited the highest antibacterial activity against wild type and streptomycin resistant Xcc with inhibition zones of 22.91 ± 0.45 and 20.28 ± 0.53, respectively. Furthermore, B. velezensis Bv-21 strain was tested for biocontrol activity against a streptomycin-resistant XccM4 in detached susceptible citrus leaves. The strain reduced the incidence of CBC by 26.30% and pathogen density of XccM4 by 81.68% over control. The results of the study strongly suggest that B. velezensis can be used as an effective and eco-friendly biocontrol agent either by itself or as an active compound, against both, the wild-type and streptomycin-resistant Xcc.

Microbial Metabolites: The Emerging Hotspot of Antiviral Compounds as Potential Candidates to Avert Viral Pandemic Alike COVID-19.

The present global COVID-19 pandemic caused by the noble pleomorphic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has created a vulnerable situation in the global healthcare and economy. In this pandemic situation, researchers all around the world are trying their level best to find suitable therapeutics from various sources to combat against the SARS-CoV-2. To date, numerous bioactive compounds from different sources have been tested to control many viral diseases. However, microbial metabolites are advantageous for drug development over metabolites from other sources. We herein retrieved and reviewed literatures from PubMed, Scopus and Google relevant to antiviral microbial metabolites by searching with the keywords "antiviral microbial metabolites," "microbial metabolite against virus," "microorganism with antiviral activity," "antiviral medicine from microbial metabolite," "antiviral bacterial metabolites," "antiviral fungal metabolites," "antiviral metabolites from microscopic algae' and so on. For the same purpose, the keywords "microbial metabolites against COVID-19 and SARS-CoV-2" and "plant metabolites against COVID-19 and SARS-CoV-2" were used. Only the full text literatures available in English and pertinent to the topic have been included and those which are not available as full text in English and pertinent to antiviral or anti-SARS-CoV-2 activity were excluded. In this review, we have accumulated microbial metabolites that can be used as antiviral agents against a broad range of viruses including SARS-CoV-2. Based on this concept, we have included 330 antiviral microbial metabolites so far available to date in the data bases and were previously isolated from fungi, bacteria and microalgae. The microbial source, chemical nature, targeted viruses, mechanism of actions and IC50/EC50 values of these metabolites are discussed although mechanisms of actions of many of them are not yet elucidated. Among these antiviral microbial metabolites, some compounds might be very potential against many other viruses including coronaviruses. However, these potential microbial metabolites need further research to be developed as effective antiviral drugs. This paper may provide the scientific community with the possible secret of microbial metabolites that could be an effective source of novel antiviral drugs to fight against many viruses including SARS-CoV-2 as well as the future viral pandemics.

Therapeutic Promises of Medicinal Plants in Bangladesh and Their Bioactive Compounds against Ulcers and Inflammatory Diseases.

When functioning properly, the stomach is the center of both physical and mental satisfaction. Gastrointestinal disorders, or malfunctioning of the stomach, due to infections caused by various biological entities and physiochemical abnormalities, are now widespread, with most of the diseases being inflammatory, which, depending on the position and degree of inflammation, have different names such as peptic or gastric ulcers, irritable bowel diseases, ulcerative colitis, and so on. While many synthetic drugs, such as non-steroidal anti-inflammatory drugs, are now extensively used to treat these diseases, their harmful and long-term side effects cannot be ignored. To treat these diseases safely and successfully, different potent medicinal plants and their active components are considered game-changers. In consideration of this, the present review aimed to reveal a general and comprehensive updated overview of the anti-ulcer and anti-inflammatory activities of medicinal plants. To emphasize the efficacy of the medicinal plants, various bioactive compounds from the plant extract, their experimental animal models, and clinical trials are depicted.

Corrigendum to "In Silico Genome-Wide Analysis of the ATP-Binding Cassette Transporter Gene Family in Soybean (Glycine max L.) and Their Expression Profiling".

[This corrects the article DOI: 10.1155/2019/8150523.].

Bacillus velezensis: A Valuable Member of Bioactive Molecules within Plant Microbiomes.

Bacillus velezensis is an aerobic, gram-positive, endospore-forming bacterium that promotes plant growth. Numerous strains of this species have been reported to suppress the growth of microbial pathogens, including bacteria, fungi, and nematodes. Based on recent phylogenetic analysis, several Bacillus species have been reclassified as B. velezensis. However, this information has yet to be integrated into a well-organized resource. Genomic analysis has revealed that B. velezensis possesses strain-specific clusters of genes related to the biosynthesis of secondary metabolites, which play significant roles in both pathogen suppression and plant growth promotion. More specifically, B. velezensis exhibits a high genetic capacity for synthesizing cyclic lipopeptides (i.e., surfactin, bacillomycin-D, fengycin, and bacillibactin) and polyketides (i.e., macrolactin, bacillaene, and difficidin). Secondary metabolites produced by B. velezensis can also trigger induced systemic resistance in plants, a process by which plants defend themselves against recurrent attacks by virulent microorganisms. This is the first study to integrate previously published information about the Bacillus species, newly reclassified as B. velezensis, and their beneficial metabolites (i.e., siderophore, bacteriocins, and volatile organic compounds).

In Silico Genome-Wide Analysis of the ATP-Binding Cassette Transporter Gene Family in Soybean (Glycine max L.) and Their Expression Profiling.

ATP-binding cassette (ABC) transporters constitute one of the largest gene families in all living organisms, most of which mediate transport across biological membranes by hydrolyzing ATP. However, detailed studies of ABC transporter genes in the important oil crop, soybean, are still lacking. In the present study, we carried out genome-wide identification and phylogenetic and transcriptional analyses of the ABC gene family in G. max. A total of 261 G. max ABC (GmABCs) genes were identified and unevenly localized onto 20 chromosomes. Referring to protein-domain orientation and phylogeny, the GmABC family could be classified into eight (ABCA-ABCG and ABCI) subfamilies and ABCG were the most abundantly present. Further, investigation of whole genome duplication (WGD) signifies the role of segmental duplication in the expansion of the ABC transporter gene family in soybean. The Ka/Ks ratio indicates that several duplicated genes are governed by intense purifying selection during evolution. In addition, in silico expression analysis based on RNA-sequence using publicly available database revealed that ABC transporters are differentially expressed in tissues and developmental stages and in dehydration. Overall, we provide an extensive overview of the GmABC transporter gene family and it promises the primary basis for the study in development and response to dehydration tolerance.