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.

Antimicrobial potential of Streptomyces sp. to the Gram positive and Gram negative pathogens.

BACKGROUND: The occurrence of drug resistant infectious disease causing microbial pathogens was highly spreaded because of the wide level application of the commercially available antimicrobial agents. However, the eradication of the microbial pathogens was of huge demand. Although, many antimicrobial compounds were commercially available in the market however the spreading of the pathogens were hugely increased. Actinomycetes produce various secondary metabolites against pathogenic bacteria and fungi. The present investigation aimed to study the antimicrobial potential of the Streptomyces sp. towards infectious diseases causing pathogens. METHODS: Culture dependable isolation techniques were followed for the isolation of the active actinomycetes isolates and the antimicrobial properties of the actinomcyetes were detected by primary screening techniques using modified starch casein agar medium. The active isolate was confirmed by various biochemical and morphological techniques. RESULTS: In this study, 10 actinomycetes were isolated and later five were selected for secondary screening and noted significant activity against Enterobacter aerogenes and Proteus mirabilis. Among the selected Streptomyces sp., ES2 showed potent activity against selected microbes and was identified as Streptomyces sp. The studied isolates were resisitant towards streptomycin (10µg), ampicillin (50µg) and ciprofloxacin (5µg). The organic solvent extracts of the promising isolate ES2 prononunced comparatively better inhibitory properties towards the studied pathogenic bacteria. CONCLUSION: Overall, the present study evidenced that the actinomycetes were promising candidate for the eradication of the pathogenic strains.

Successful treatment of tuberculous and nocardial arthritis in a hemodialysis patient with subsequent kidney transplant.

A 42-year-old physician on maintenance hemodialysis for chronic renal failure presented with intermittent fever and arthritis of the right knee. Synovectomy specimen of the right knee showed caseating granuloma, consistent with tuberculosis, which was successfully treated with a four-drug regimen of anti-tuberculous therapy. Subsequently, he had a recurrent effusion of the same joint, which on aspiration showed nocardial infection. He was treated with a combination therapy (sulfamethoxazole-trimethoprim and amoxicillin) for four months. He underwent a successful living-related transplant two months later, and was doing well on triple immunosuppression one year after transplantation.