Extracellular facile biosynthesis, characterization and stability of gold nanoparticles by Bacillus licheniformis.

CONTEXT: The development of a reliable, eco-friendly process for synthesis of gold nanoparticles (AuNPs) has gained impetus in recent years to counter the drawbacks of chemical and physical methods. OBJECTIVE: This study illustrates simple, green synthesis of AuNPs in vitro using cell lysate supernatant (CLS) of non-pathogenic bacteria and to investigate its potential antimicrobial activity. MATERIALS AND METHODS: Gold nanoparticles were synthesized by the reduction of precursor AuCl4- ions using the CLS of Bacillus licheniformis at 37°C upon 24 h of incubation. The nanoparticles were characterized for their morphology, particle size, optical absorption, zeta potential, and stability. Further the antimicrobial activity was assayed using cup-plate method. RESULTS: The process of biosynthesis was extracellular and the gold ions were reduced to stable nanogold of average size 38 nm. However, upon storage of AuNPs for longer duration at room temperature stability was influenced in terms of increase in particle size and decrease in zeta potential with respect to as synthesized nanoparticles. SEM micrographs revealed the spherical shape of AuNPs and EDX analysis confirmed the presence of gold in the sample. Also clear zone of inhibition was observed against Bacilllus subtilis MTCC 8364, Pseudomonas aeruginosa MTCC 7925, and Escherichia coli MTCC 1698 confirming the antimicrobial activity of AuNPs. DISCUSSION: The bioprocess under study was simple and less time consuming as compared to other methods as the need for harvesting AuNPs from within the microbial cells via downstream process will be eliminated. Nanoparticles exhibited good stability even in absence of external stabilizing agents. AuNPs showed good antimicrobial activity against several Gram-negative and Gram-positive pathogenic bacteria. CONCLUSION: The extracellular biosynthesis from CLS may serve as a suitable alternative for large scale synthesis of gold nanoparticles in vitro. The synthesis from lysed bacterial cell strongly suggests that exposure of microbial whole cells to the gold solution for nanoparticle formation is not necessary and that microorganism even in lysed state retained its bioreduction potential. Further the potential of biologically synthesized AuNPs as antimicrobial agents will be of great commercial importance.

Meropenem: a potent drug against superbug as unveiled through bioinformatics approaches.

Global spread of multi-drug resistant bacteria like Klebsiella pneumoniae and Escherichia coli have raised the alarm for researchers and doctors throughout the world. This new mechanism of resistance and the ability of ndm-1 gene to be transferred between the species may end the era of antibiotics treatment. Carbapenems are reliable drugs against many multi-resistant gram-negative pathogens. A 3-D homology model of NDM-1 was built and analysed for elucidation of functional site and binding interactions. This study revealed that meropenem has good interaction with the active sites of the receptor that could retard the spread of antibiotic resistant bacteria.

Comparative analysis of different DNA-binding drugs for leishmaniasis cure: a pharmacoinformatics approach.

Several experiments have been performed to test DNA-binding drugs to cure Leishmania infection. However, there are no details of pharmacoinformatics study. Herein, we have selected a good number of compounds from experimentally verified studies and performed a comparative analysis based on pharmacoinformatics techniques. In silico docking study was performed to observe the molecular level interactions of these known ligands with the DNA receptor by automated computational docking using Glide. A comparison between the calculated interaction energies and in silico ADME/T study was made. In agreement with drug likeness rules, our study suggests that seco-hydroxy-aza-CBI-TMI (compound 4b; GScore, -12.058) is a potential molecule for targeting the DNA to cure leishmaniasis.

Homology modeling and function prediction of hABH1, involving in repair of alkylation damaged DNA.

Inhibition of DNA repair mechanism through alkylating agents in tumor cells is an important method for cancer treatment. Alkylation damage repair gene AlkB was first reported in E. coli. In human and other mammals eight distinguishing homologs of AlkB were detected and are known as hABH1 to hABH8. Crystal structures of hABH2 and hABH3 elucidated the role of human AlkB homologs involved in DNA and RNA repair pathways. No crystal structure of hABH1 is available for the detailed study on the nature and function of the molecule. In the present work we performed homology modeling and different tertiary structure based study on human AlkB homolog hABH1. hABH1.B99990005.pdb, out of five models generated using the program modeler 9v7 and validated with Ramachandran plot showed that 97.9% residues were in the favored and additional allowed region and less residues in disallowed region, which is the best among all models. Functions of the selected model were studied in terms of cation binding, transition metal ion binding and metal ion binding function with oxidoreductase activity. Two functional sites and one conserved cluster were detected in the protein. Ligand binding residue prediction showed four ligand clusters with 17 ligands in cluster 1. In this cluster seven Fe(2+) heterogen counts were detected. Most significantly, predicted iron-binding motif in hABH1 was found as His231-X-Asp233-XnHis287 which corresponds to His131-XAsp133-Xn-His187 in AlkB of E. coli homologue. This shows the similar pattern of aspartic acid and histidine residues in the functional part of the protein both in human and E. coli. These results can be used further to design inhibitors aiding chemotherapy and cancer related diseases.

A molecular docking study of anticancer drug paclitaxel and its analogues.

Present study was aimed at finding a better alternative to paclitaxel, an anticancer chemotherapeutic drug. Two targets, tubulin beta-1 chain and apoptosis regulator Bcl-2 protein (202F) were used in the study. Of these, structure of tubulin beta-1 chain is not known and that of Bcl-2 was taken from protein data bank with ID 202F. Tertiary structure model of tubulin beta-1 chain was predicted and validated. The validated 3D structure of tubulin beta-1 chain and Bcl-2 protein was taken to study their interaction with paclitaxel. Molecular docking of paclitaxel and its analogues was performed with these targets separately. Results showed that out of 84 analogues taken from PubChem, CID_44322802 had glide score of -9.62, as compared to -5.86 of paclitaxel with tubulin beta-1 chain. It was also observed that CID_9919057 had glide score of -9.0, as compared to -8.24 of paclitaxel with Bcl-2 protein. However, further experimental and clinical verification is needed to establish these analogues as drug.

Comparative multivariate analysis of codon and amino acid usage in three Leishmania genomes.

Multivariate analysis of codon and amino acid usage was performed for three Leishmania species, including L. donovani, L. infantum and L. major. It was revealed that all three species are under mutational bias and translational selection. Lower GC12 and higher GC3S in all three parasites suggests that the ancestral highly expressed genes (HEGs), compared to lowly expressed genes (LEGs), might have been rich in AT-content. This also suggests that there must have been a faster rate of evolution under GC-bias in LEGs. It was observed from the estimation of synonymous/non-synonymous substitutions in HEGs that the HEG dataset of L. donovani is much closer to L. major evolutionarily. This is also supported by the higher dN value as compared to dS between L. donovani and L. major, suggesting the conservation of synonymous codon positions between these two species and the role of translational selection in shaping the composition of protein-coding genes.