Putative Role of Anti-microbial Peptide Recovered from Lactiplantibacillus spp. in Biocontrol Activity.

Antimicrobial peptides (AMPs) stand as a promising alternative to conventional pesticides, leveraging a multifaceted approach to combat plant pathogens. This study focuses on identifying and characterizing the AMP produced by Lactiplantibacillus argentoratensis strain IT, demonstrating potent antibacterial activity against various harmful microorganisms. Evaluation of AMPs' antibacterial activity was conducted through an agar well diffusion assay, a reliable method for assessing secondary metabolite antimicrobial efficacy. The study unveils the antimicrobial potential of the purified extract obtained from Lactiplantibacillus argentoratensis IT, isolated from goat milk. Notably, the AMP exhibited robust antibacterial activity against phytopathogens affecting solanaceous crops, including the Gram-negative Ralstonia solanacearum. Expression conditions and purification methods were optimized to identify the peptide's mass and sequence, utilizing LC-MS and SDS-PAGE. This paper underscores the application potential of Lactiplantibacillus spp. IT as a biocontrol agent for managing bacterial infectious diseases in plants. Results indicate optimal AMP production at 37 °C, with a culture broth pH of 5 during fermentation. The obtained peptide sequence corresponded to peaks at 842.5 and 2866.4 m/z ratio, with a molecular weight of approximately 5 kDa according to tricine SDS-PAGE analysis. In conclusion, this study lays the foundation for utilizing Lactiplantibacillus spp. IT derived AMPs in plant biocontrol strategies, showcasing their efficacy against bacterial phytopathogens. These findings contribute valuable insights for advancing sustainable agricultural practices.

'Synthesis, antiviral activity, molecular docking, and molecular dynamics studies of ethoxy phthalimide pyrazole derivatives against Cytomegalovirus and Varicella-Zoster virus: potential consequences and strategies for developing new antiviral treatments'.

Substituted ethoxy phthalimide pyrazole derivatives (6a-e) have been produced using a one-pot synthesis technique. Spectral analysis was used to establish the molecular structure of the synthesized compounds, and they were examined in silico and in vitro for their ability to bind to and inhibit replication of the AD-169 strain, the Davis strain of CMV, the OKA strain and the 07/1 strain of Varicella-Zoster virus (VZV). Molecular Docking was used to estimate the binding mechanism and energy of compounds 4, 6a-e to their respective target proteins, thymidine kinase (TK), Varicella-Zoster protease (VZP) of VZV and tegument protein pp71 (TPpp71) of Cytomegalovirus (CMV). The MIC50 and EC50 were utilized to evaluate the antiviral and cytotoxic activities of test compounds in human embryonic lung (HEL) cells against the two reference medicines, Ganciclovir and Acyclovir. The chemicals studied showed a high affinity for binding sites and near binding sites of target proteins by generating H-bonds, carbon-hydrogen bonds, π-anion, π-sulfur, π-sigma, alkyl and π-alkyl interactions. All of the test compounds (6a-e) had higher binding energy than the standard medications. The ADME/T data suggests that these potential inhibitors are less toxic. Drug-protein complexes are structurally compact and demonstrate minimal conformational change in molecular dynamics (MDs) simulations, indicating stability and stiffness. MM-PBSA and post-simulation analysis can predict lead compound active cavity binding stability. By inhibiting multitargeted proteins, these synthetic compounds may improve antiviral therapy. Our research suggests that these unique synthesized chemicals may be useful and accessible adjuvant antiviral therapy for Varicella Zoster and CMV. HighlightsTwo components synthesis of substituted ethoxy phthalimide pyrazole derivatives (6a-e).Tested compounds (6a-e) have antiviral and cytotoxicity activity against CMV and Varicella-Zoster virus (VZV) in HEL cells.Compounds bind to TK, Varicella-Zoster protease (VZP) of VZV, and modeled TPpp71 of Cytomegalovirus (CMV).In comparison to reference drugs, compounds have strong binding free energy and interactions with VZV and CMV protein complexes.The RMSD, RMSF, Rg, residual correlative motion (RCM), No. of hydrogen bonds, protein secondary structure content, per-residue protein secondary structure and MM/PBSA energy calculated for the selected compound with thymidine kinase (TK), VZP of VZV, and modeled tegument protein pp71 (TPpp71) of CMV through MD simulation studies for 50 ns.In comparison to the two reference drugs, ligands/compounds were found to meet the Lipinski rule of five and to have strong biological activity.Communicated by Ramaswamy H. Sarma.

Bioprospecting of novel ligninolytic bacteria for effective bioremediation of agricultural by-product and synthetic pollutant dyes.

Lignin is a significant renewable carbon source that needs to be exploited to manufacture bio-ethanol and chemical feedstocks. Lignin mimicking methylene blue (MB) dye is widely used in industries and causes water pollution. Using kraft lignin, methylene blue, and guaiacol as a full carbon source, 27 lignin-degrading bacteria (LDB) were isolated from 12 distinct traditional organic manures for the current investigation. The ligninolytic potential of 27 lignin-degrading bacteria was assessed by qualitative and quantitative assay. In a qualitative plate assay, the LDB-25 strain produced the largest zone, measuring 6.32 ± 0.297, on MSM-L-kraft lignin plates, while the LDB-23 strain produced the largest zone, measuring 3.44 ± 0.413, on MSM-L-Guaiacol plates. The LDB-9 strain in MSM-L-kraft lignin broth was able to decolorize lignin to a maximum of 38.327 ± 0.011% in a quantitative lignin degradation assay, which was later verified by FTIR assay. In contrast, LDB-20 produced the highest decolorization (49.633 ± 0.017%) in the MSM-L-Methylene blue broth. The highest manganese peroxidase enzyme activity, measuring 6322.314 ± 0.034 U L-1, was found in the LDB-25 strain, while the highest laccase enzyme activity, measuring 1.5105 ± 0.017 U L-1, was found in the LDB-23 strain. A preliminary examination into the biodegradation of rice straw using effective LDB was carried out, and efficient lignin-degrading bacteria were identified using 16SrDNA sequencing. SEM investigations also supported lignin degradation. LDB-8 strain had the highest percentage of lignin degradation (52.86%), followed by LDB-25, LDB-20, and LDB-9. These lignin-degrading bacteria have the ability to significantly reduce lignin and lignin-analog environmental contaminants, therefore they can be further researched for effective bio-waste management mediated breakdown.

"In silico identification of ethoxy phthalimide pyrazole derivatives as IL-17A and IL-18 targeted gouty arthritis agents".

Two proinflammatory cytokines, IL17A and IL18, are observed to be elevated in the serum of gout patients and they play a crucial role in the development and worsening of inflammation, which has severe effects. In present study, we have combined molecular docking, molecular dynamics studies and MM-PBSA analysis to study the effectiveness of ethoxy phthalimide pyrazole derivatives (series 3a to 3e) as potential inhibitors against cytokines IL17A and IL18 as a druggable targets. The binding energy of the docked series ranges from -13.5 to -10.0 kcal/mol and extensively interacts with the amino acids in the active pocket of IL17A and IL18. Compound 3e had the lowest binding energy with IL17A at -12.6 kcal/mol compared to control allopurinol (3.32 kcal/mol). With IL18, compound 3a seems to have the lowest binding energy of -9.6 kcal/mol compared to control allopurinol (3.18 kcal/mol). In MD simulation studies, compound 3a forms a stable and energetically stabilized complex with the target protein. Depending on properties of the bound IL17A-3a and IL18-3a complexes was compared by means of MM-PBSA analysis. These derivatives can be used as a scaffold to develop promising IL17A and IL18 inhibitors to assess their potential for gouty arthritis and other related diseases. Communicated by Ramaswamy H. Sarma.

Root Exudates: Mechanistic Insight of Plant Growth Promoting Rhizobacteria for Sustainable Crop Production.

The breaking silence between the plant roots and microorganisms in the rhizosphere affects plant growth and physiology by impacting biochemical, molecular, nutritional, and edaphic factors. The components of the root exudates are associated with the microbial population, notably, plant growth-promoting rhizobacteria (PGPR). The information accessible to date demonstrates that PGPR is specific to the plant's roots. However, inadequate information is accessible for developing bio-inoculation/bio-fertilizers for the crop in concern, with satisfactory results at the field level. There is a need to explore the perfect candidate PGPR to meet the need for plant growth and yield. The functions of PGPR and their chemotaxis mobility toward the plant root are triggered by the cluster of genes induced by the components of root exudates. Some reports have indicated the benefit of root exudates in plant growth and productivity, yet a methodical examination of rhizosecretion and its consequences in phytoremediation have not been made. In the light of the afore-mentioned facts, in the present review, the mechanistic insight and recent updates on the specific PGPR recruitment to improve crop production at the field level are methodically addressed.

Identification of 1, 2, 4-Triazine and Its Derivatives Against Lanosterol 14-Demethylase (CYP51) Property of Candida albicans: Influence on the Development of New Antifungal Therapeutic Strategies.

This research aims to find out whether the 1, 2, 4-triazine and its derivatives have antifungal effects and can protect humans from infection with Candida albicans. Molecular docking and molecular dynamic simulation are widely used in modern drug design to target a particular protein with a ligand. We are interested in using molecular docking and molecular dynamics modeling to investigate the interaction between the derivatives of 1, 2, 4-triazine with enzyme Lanosterol 14-demethylase (CYP51) of Candida albicans. The inhibition of Candida albicans CYP51 is the main goal of our research. The 1, 2, 4-triazine and its derivatives have been docked to the CYP51 enzyme, which is involved in Candida albicans Multidrug Drug Resistance (MDR). Autodock tools were used to identify the binding affinities of molecules against the target proteins. Compared to conventional fluconazole, the molecular docking results indicated that each drug has a high binding affinity for CYP51 proteins and forms unbound interactions and hydrogen bonds with their active residues and surrounding allosteric residues. The docking contacts were made using a 10 ns MD simulation with nine molecules. RMSD, RMSF, hydrogen bonds, and the Rg all confirm these conclusions. In addition, these compounds were expected to have a favorable pharmacological profile and low toxicity. The compounds are being offered as scaffolds for the development of new antifungal drugs and as candidates for future in vitro testing.

Unlocking SGK1 inhibitor potential of bis-[1-N,7-N, pyrazolo tetraethoxyphthalimido{-4-(3,5-Dimethyl-4-(spiro-3-methylpyazolo)-1,7-dihydro-1H-dipyrazolo[3,4-b;4',3'-e]pyridin-8-yl)}]p-disubstituted phenyl compounds: a computational study.

SGK1 (Serum and Glucocorticoid Regulated Kinase 1), a serine/threonine kinase that is activated by various stimuli, including serum and glucocorticoids. It controls inflammation, apoptosis, hormone release, neuro-excitability and cell proliferation, all of which play an important role in cancer progression and metastasis. SGK1 was recently proposed as a potential drug target for cancer, diabetes, and neurodegenerative diseases. In this study, molecular docking, physiochemical, toxicological properties and molecular dynamic simulation of the Bis-[1-N,7-N, Pyrazolo tetraethoxyphthalimido{-4-(3,5-Dimethyl-4-(spiro-3-methylpyazolo)-1,7-dihydro-1H-dipyrazolo[3,4-b;4',3'-e]pyridin-8-yl)}]p-disubstituted phenyl compoundsand reference EMD638683 against new SGK1 target protein. Compared to the reference inhibitor EMD638683, we choose the best compounds (series 2-6) based on the binding energy (in the range from -11.0 to -10.6 kcal/mol). With the exception of compounds 2 and 6, none of the compounds posed a risk for AMES toxicity or carcinogenicity due to their toxicological properties. 100 ns MD simulation accompanied by MM/PBSA energy calculations and PCA. According to MD simulation results, the binding of compounds 3, 4 and 5 stabilizes the SGK1 structure and causes febrile conformational changes compared to EMD638683. As a result of this research, the final selected compounds 3, 4 and 5 can be used as scaffolds to develop promising SGK1 inhibitors for the treatment of related diseases such as cancer.Communicated by Ramaswamy H. Sarma.

Molecular docking and simulation studies of flavonoid compounds against PBP-2a of methicillin-resistant Staphylococcus aureus.

Methicillin-Resistant Staphylococcus aureus (MRSA), a pathogenic bacterium that causes life-threatening outbreaks such as community-onset and nosocomial infections as emerging 'superbug'. Time and motion study of its virulent property developed resistance against most of the antibiotics such as Vancomycin. Thereby, to curb this problem entails the development of new therapeutic agents. Plant-derived antimicrobial agents have recently piqued people's interest, so in this research, 186 flavonoids compound selected to unmask the best candidates that can act as potent inhibitors against the Penicillin Binding Protein-2a (PBP-2a) of MRSA. Molecular docking performed using PyRx and GOLD suite to determine the binding affinities and interactions between the phytochemicals and the PBP-2a. The selected candidates strongly interact with the different amino acid residues. The 30 ns molecular dynamics (MD) simulations with five top-ranked compounds such as Naringin, Hesperidin, Neohesperidin, Didymin and Icariin validated the docking interactions. These findings are also strongly supported by root-mean-square deviation, root-mean-square fluctuation and the radius of gyration. ADME/T analysis demonstrates that these candidates appear to be safer inhibitors. Our findings point to natural flavonoids as a promising and readily available source of adjuvant antimicrobial therapy against resistant strains in the future.Communicated by Ramaswamy H. Sarma.

Screening and Optimization of Zinc Removal Potential in Pseudomonas aeruginosa-HMR1 and its Plant Growth-Promoting Attributes.

The soil samples of old Zawar mine sites were sandy texture, basic, electric conductivity range from 16 to 59 dSm-1 with a high content of heavy metals of Zn, Pb, Cd, and Fe, indicating poor soil-health. Two bacterial isolates Pseudomonas aeruginosa HMR1 and P. aeruginosa HMR16 (GenBank-accession-number KJ191700 and KU174205, respectively), differed in the Phylogenetic tree based on 16S-rDNA sequences. HMR1 isolate showed the high potential of Plant growth-promoting attributes like IAA, Phosphate-solubilization, Exopolysaccharide production, and Proline activities at high concentration of Zn augmented nutrient media after 24 h, followed by HMR1 + HMR16 and HMR16. Both isolates were survived at 100 ppm Zn (w/v) concentration, followed by Pb, Cd, and Fe. Linear RL value from Langmuir and Freundlich isotherms revealed that the suitable condition of Zn adsorption by HMR1 was at pH8 with 40°C. The value of r2 from pseudo-second-order kinetics and Transmission-Electron-Microscopic analysis confirmed Zn adsorption by HMR1.

Polyphasic Characterization of Plant Growth Promoting Cellulose Degrading Bacteria Isolated from Organic Manures.

In the present study, twenty seven cellulose-degrading bacteria (CDB) were isolated from various organic manures and their cellulolytic activities were determined. The bacterial isolate CDB-26 showed the highest cellulolytic index, released 0.507 ± 0.025 mg/ml glucose and produced 0.196 ± 0.014 IU/ml cellulase enzyme under in vitro conditions. Biochemically, all the 27 isolates showed difference in the 6 biochemical tests performed. Further, all the 27 CDB isolates were subjected to various plant growth-promoting activities, and all CDB strains were positive for IAA production, GA3 production and siderophore production, whereas 19 strains were positive for ACC deaminase activity, 21 strains showed NH3 production and 19 strains were positive for HCN production. Out of 27 CDB isolates, 18 isolates were able to solubilize phosphate, 21 isolates were able to solubilize potash and 10 CDB isolates were found positive for silica solubilization. The molecular diversity among different CDB isolates was studied through ARDRA and demonstrated very high genetic diversity among these bacteria. The in vitro cellulose-degradation potential of these CDB isolates using vegetable waste as substrate were also assessed, and the 3 CDB isolates viz. Serratia surfactantfaciens (CDB-26), Stenotrophomonas rhizophila (CDB-16) and Pseudomonas fragi (CDB-5) showed the highest cellulose-degrading potential under in vitro conditions. Hence, the cellulolytic microbes isolated in the present study could be used for effective bioconversion of plant biomasses into enriched compost.

Microbial Fabrication of Zinc Oxide Nanoparticles and Evaluation of Their Antimicrobial and Photocatalytic Properties.

Zinc oxide (ZnO) nanoparticles have attracted significant interest in a number of applications ranging from electronics to biomedical sciences due to their large exaction binding energy (60 meV) and wide bandgap of 3.37 eV. In the present study, we report the low-cost bacterium based "eco-friendly" efficient synthesis of ZnO nanoparticles by using the zinc-tolerant bacteria Serratia nematodiphila. The physicochemical characterization of ZnO nanoparticles was performed by employing UV-vis spectroscopy, XRD, TEM, DLS, Zeta potential, and Raman spectroscopy. The antimicrobial and antifungal studies were investigated at different concentrations using the agar well-diffusion method, whereby the microbial growth rate decreases with the increase in nanoparticle concentration. Further, photocatalytic performance studies were conducted by taking methyl orange (MO) as a reference dye.

Zinc tolerant plant growth promoting bacteria alleviates phytotoxic effects of zinc on maize through zinc immobilization.

The increasing heavy metal contamination in agricultural soils has become a serious concern across the globe. The present study envisages developing microbial inoculant approach for agriculture in Zn contaminated soils. Potential zinc tolerant bacteria (ZTB) were isolated from zinc (Zn) contaminated soils of southern Rajasthan, India. Isolates were further screened based on their efficiency towards Zn tolerance and plant growth promoting activities. Four strains viz. ZTB15, ZTB24, ZTB28 and ZTB29 exhibited high degree of tolerance to Zn up to 62.5 mM. The Zn accumulation by these bacterial strains was also evidenced by AAS and SEM-EDS studies. Assessment of various plant growth promotion traits viz., IAA, GA3, NH3, HCN, siderophores, ACC deaminase, phytase production and P, K, Si solubilization studies revealed that these ZTB strains may serve as an efficient plant growth promoter under in vitro conditions. Gluconic acid secreted by ZTB strains owing to mineral solubilization was therefore confirmed using high performance liquid chromatography. A pot experiment under Zn stress conditions was performed using maize (Zea mays) variety (FEM-2) as a test crop. Zn toxicity reduced various plant growth parameters; however, inoculation of ZTB strains alleviated the Zn toxicity and enhanced the plant growth parameters. The effects of Zn stress on antioxidant enzyme activities in maize under in vitro conditions were also investigated. An increase in superoxide dismutase, peroxidase, phenylalanine ammonia lyase, catalase and polyphenol oxidase activity was observed on inoculation of ZTB strains. Further, ZIP gene expression studies revealed high expression in the ZIP metal transporter genes which were declined in the ZTB treated maize plantlets. The findings from the present study revealed that ZTB could play an important role in bioremediation in Zn contaminated soils.

Zinc biosorption, biochemical and molecular characterization of plant growth-promoting zinc-tolerant bacteria.

Zinc plays a key role in plant nutrition at low levels; however, at higher concentrations Zn ions can be highly phytotoxic and plant growth-promoting rhizobacteria can be used to reduce such metal toxicity. In the present investigation we had reported the zinc biosorption and molecular characterization of plant growth-promoting zinc-tolerant bacteria. Initially, thirty bacteria having zinc solubilizing ability were screened for MIC against zinc ion and displayed high value of MIC ranging from 2.5 to 62.5 mM. Biochemically, all the 30 isolates showed significant difference in the 6 biochemical tests performed. The molecular diversity studies based on the repetitive DNA PCR viz, REP, ERIC and BOX elements showed significant genetic diversity among these 30 zinc-tolerant bacteria. These ZTB strains also showed multiple PGP activities and all ZTB strains were found positive for production of IAA, GA3 and ammonia, whereas 24 were found positive for ACC deaminase activity, 8 showed siderophore production and 9 ZTB isolates were positive for HCN production. Out of 30 isolates, 24 showed phosphorus solubilization activity, 30 showed potash solubilization, 15 showed silica solubilization and 27 showed phytase production activities. All the 30 ZTB stains showed zinc solubilization up to 0.25% insoluble ZnO in the medium, whereas at 2% ZnO in MSM only 12 isolates showed solubilization which were further selected for zinc biosorption and pot studies. The heavy metal removal studies revealed that ZTB stains were able to remove zinc ions effectively from the medium efficiently and the highest zinc biosorption (< 90%) was recorded with the bacterial strain Z-15. Further, the inoculation of ZTB strains under zinc stress conditions (pot containing 1000 mg/kg Zn) resulted in significant increase of shoot length, root length and total chlorophyll content in maize seedlings compared with the uninoculated control. The partial 16S rDNA sequence of the potential ZTB isolates viz. Z-15, Z-24, Z-28 and Z-29 revealed their identity as Serratia sp. The ability of these zinc-tolerant bacteria to tolerate the toxic level of zinc may serve as suitable candidates for developing microbial formulations for the growth of crop plants in Zn-contaminated areas.