Antibacterial and biofilm disruptive nonribosomal lipopeptides from Streptomyces parvulus against multidrug-resistant bacterial infections.

BACKGROUND: In recent years, new drugs for the treatment of various diseases, thereby the emergence of antimicrobial resistance tremendously increased because of the increased consumption rate of various drugs. However, the irrational use of antibiotics increases the microbial resistance along with that the frequency of mortality associated with infections is higher. Broad-spectrum antibiotics were effectively against various bacteria and the unrestricted application of antibiotics lead to the emergence of drug resistance. The present study was aimed to detect the antibacterial properties of lipopeptide novel drug producing Streptomyces parvulus. METHODS: A lipopeptide-producing S. parvulus was isolated from the soil sample. The inhibitory effect of lipopeptide was detected against Gram-positive and Gram-negative bacteria. Bactericidal activity and minimum inhibitory concentration (MIC) were assayed. The IC50 value was analysed against ovarian and human melanoma cell lines. The experimental mouse model was infected withKlebsiella pneumoniae and treated with lipopeptide and bactericidal activity was determined. RESULTS: The results indicated that the antibacterial activity of lipopeptide ranges from 13 ± 1 mm to 32 ± 2 mm against Gram-positive and Gram-negative strains. The lowest MIC value was noted as 1.5 ± 0.1 µg/mL against K. pneumoniae and the highest against E. aerogenes (7.5 ± 0.2 µg/mL). The IC50 value was considerably high for the ovarian cell lines and human melanoma cell lines (426 µg/mL and 503 µg/mL). At 25 µg/mL concentration of lipopeptide, only 16.4% inhibition was observed in the ovarian cell line whereas 20.2% inhibition was achieved at this concentration in the human melanoma cell line. Lipopeptide inhibited bacterial growth and was completely inhibited at a concentration of 20 µg/mL. Lipopeptide reduced bacterial load in experimental mice compared to control (p < 0.05). CONCLUSION: Lipopeptide activity and its non-toxic nature reveal that it may serve as a lead molecule in the development of a novel drug.

Molecular docking of monkeypox (mpox) virus proteinase with FDA approved lead molecules.

BACKGROUND: Monkeypox virus (mpox) disease is caused by a double-stranded DNA virus from the Poxviridae family. The mpox virus showed structural similarity with smallpox virus disease. The recent outbreak of mpox infection in the rest of African countries causes public health issues of increased pandemic potential. Mpox virus is involved in the viral replication cycle through the biocatalytic reaction of precursor polyproteins cleavage. OBJECTIVES: The main objective of the study was to analyze the molecular interactions between mpox and FDA-approved drugs. METHODS: The primary and secondary structure of the protein was retrieved and FDA approved drug was screened using AutoDock. The best hit was analyzed and the molecular interactions were studied. Model validation analyzes the peptide, energy of hydrogen bonds, steric conflicts and bond planarity. Z-score was calculated using ProSA-web tool and the score tested the native fold from other alternative folds. RESULTS: The confidence level of the submitted amino acids was> 80 % and the maximum confidence score for a single template was 98.2 %. The generated proteinase model was subjected to analyze the distribution of atoms and the using ERRAT server. The overall quality score was 88.535 and this value represents the amino acid percentage with anticipated error value and the value falling below the rejection limit. The Z-score of this study result was within the Z-score range (-4.17) validated for native enzymes. The binding pockets of the enzyme were determined in this study and two binding pockets were predicted using the automatic online tool using the web server. The selected FDA-approved drugs were ordered based on their minimum binding energy to the proteinase. CONCLUSIONS: Molecular docking studies revealed the involvement of various hydrophobic interactions between FDA-approved drugs and amino acid residues of monkeypox virus proteinase.

In vitro fibrinolytic activity of an enzyme purified from Bacillus amyloliquefaciens strain KJ10 isolated from soybean paste.

A fibrinolytic protease secreting producing Bacillus amyloliquefaciens strain KJ10 was initially screened from the fermented soybean. Maximum productivity was obtained in the culture medium after 40 h incubation, 34 °C incubation temperature at pH 8.0. Fibrinolytic protease production was enhanced in the culture medium with 1% sucrose (3712 ± 52 U/mL), 1% (w/v) yeast extract (3940 ± 28 U/mL) and 0.1% MgSO4 (3687 ± 38 U/mL). Enzyme was purified up to 22.9-fold with 26%recovery after Q-Sepharose HP column chromatography. After three steps purification, enzyme activity was 1606U/mg and SDS-PAGE analysis revealed 29 kDa protein and enzyme band was detected by zymograpy. Enzyme was highly active at pH 8.0, at wide temperature ranges (40 °C - 55 °C) and was activated by Mn2+ (102 ± 3.1%) and Mg2+ (101.4 ± 2.9%) ions. The purified fibrinolytic enzyme was highly specific against N-Suc-Ala-Ala-Pro-Phe-pNA (189 mmol/min/mL) and clot lytic activity reached 28 ± 1.8% within 60 minin vitro. The purified fibrinolytic enzyme showed least erythrocytic lysis activity confirmed safety to prevent various health risks, including hemolytic anemia. Based on this study, administration of fibrinolytic enzyme from B. amyloliquefaciens strain KJ10 is safe for clinical applications.

Spectral characterization of hydroxyapatite extracted from Black Sumatra and Fighting cock bone samples: A comparative analysis.

At present, chicken business is occupying a major portion in the market and huge amount of bone wastes are dumped into the open places lead in environmental pollution. In this analysis, natural hydroxyapatite was extracted by thermal calcination process at different temperature ranges from 700 °C, 900 °C and 1100 °C and compared its spectral characteristics. The crystalline nature, functional groups and morphological characteristics of hydroxyapatite obtained from both bone samples were studied using XRD, FTIR and SEM analysis. The crystallite size, lattice parameters, specific surface area, volume and degree of crystallinity were measured using XRD data. The mean grain size of Black Sumatra and Fighting Cock bone hydroxyapatite was 62.67 nm and 31.34 nm respectively. The FTIR spectrum showed major peaks at 634.58 cm-1 and 470.63 cm-1, 1413.82 cm-1 and 1460 cm-1 indicates the presence of carbonate group and phosphate groups in both samples. The SEM micrograph confirmed the existence of maximum pores in matrix of fighting cock bone than Black Sumatra bone sample. Thus, the comparative analysis concluded that nano-sized hydroxyapetite obtained from bone wastes of fighting cock can be utilized as a low-cost biomaterial for the production of various implant coating materials and substitute for ceramics in bones and dentistry applications.

Identification of phytochemical components from Aerva lanata (Linn.) medicinal plants and its in-vitro inhibitory activity against drug resistant microbial pathogens and antioxidant properties.

This study aimed to determine the phytochemical components, microbial inhibitory effectiveness and antioxidant properties of Aerva lanata plant extracts. The whole plant showed various medicinal applications in folklore and traditional medicine in various parts of the world. The organic extracts such as ethanol, ethyl acetate, chloroform, acetone, water and methanol were subjected for various phytochemical analysis and confirmed for the existence of flavonoids, glycosides, terpenoids and alkaloid containing components. Alternatively, the extracts were performed for the antibacterial activities against the microbial pathogens and antioxidant properties. Results indicated that, the solvent extracts showed prominent activity against the tested strains. The MIC concentrations of plant were detected from 5 mg/ml to 40 mg/ml. The plant extract was highly effective against E. coli and E. aerogenes and the MIC was 5 mg/ml. In addition, the extracts noted promising antioxidant activities. The antioxidant activities were dose dependent manner. In conclusion, A. lanata extracts showed that significant major phytochemicals and effective antioxidant and anti-microbial properties.

Potential Effect of Bacopa monnieri on Nitrobenzene Induced Liver Damage in Rats.

The study was designed to evaluate the hepatoprotective activity of ethanolic extract of Bacopa monnieri in acute experimental liver injury induced by Nitrobenzene in rats. The extract at the dose of 200 mg/kg body weight was administered orally once every day for 10 days. The increased serum marker enzymes, Aspartate transaminase, Alanine transaminase and alkaline phosphatase were restored towards normalization significantly by the extract. Significant increase in SOD, CAT and GPx was observed in extract treated liver injured experimental rats. Histopathological examination of the liver tissues supported the hepatoprotection. It is concluded that the ethanolic extract of Bacopa monieri plant possess good hepatoprotective activity.