Identification of a potential inhibitor for New Delhi metallo-ß-lactamase 1 (NDM-1) from FDA approved chemical library- a drug repurposing approach to combat carbapenem resistance.

Superbugs producing New Delhi metallo-ß-lactamase 1 (NDM-1) enzyme is a growing crisis, that is adversely affecting the global health care system. NDM-1 empowers the bacteria to inactivate entire arsenal of ß-lactam antibiotics including carbapenem (the last resort antibiotic) and remains ineffective to all the available ß lactamase inhibitors used in the clinics. Limited therapeutic option available for rapidly disseminating NDM-1 producing bacteria makes it imperative to identify a potential inhibitor for NDM-1 enzyme. With drug repurposing approach, in this study, we used virtual screening of available Food and Drug Administration (FDA) approved chemical library (ZINC12 database) and captured 'adapalene' (FDA drug) as a potent inhibitor candidate for NDM-1 enzyme. Active site docking with NDM-1, showed adapalene with binding energy -9.21 kcal/mol and interacting with key amino acid residues (Asp124, His122, His189, His250, Cys208) in the active site of NDM-1. Further, molecular dynamic simulation of NDM-1 docked with the adapalene at 100 ns displayed a stable conformation dynamic, with relative RMSD and RMSF in the acceptable range. Subsequently, in vitro enzyme assays using recombinant NDM-1 protein demonstrated inhibition of NDM-1 by adapalene. Further, the combination of adapalene plus meropenem (carbapenem antibiotic) showed synergistic effect against the NDM-1 producing carbapenem (meropenem) resistant clinical isolates (Escherichia coli and Klebsiella pneumoniae). Overall, our data indicated that adapalene can be a potential inhibitor candidate for NDM-1 enzyme that can contribute to the development of a suitable adjuvant to save the activity of carbapenem antibiotic against infections caused by NDM-1 positive gram-negative bacteria. Communicated by Ramaswamy H. Sarma.

In Vitro Antibacterial Activity of Green Synthesized Silver Nanoparticles Using Mangifera indica Aqueous Leaf Extract against Multidrug-Resistant Pathogens.

An estimated 35% of the world's population depends on wheat as their primary crop. One fifth of the world's wheat is utilized as animal feed, while more than two thirds are used for human consumption. Each year, 17-18% of the world's wheat is consumed by China and India. In wheat, spot blotch caused by Bipolaris sorokiniana is one of the major diseases which affects the wheat crop growth and yield in warmer and humid regions of the world. The present work was conducted to evaluate the effect of green synthesized silver nanoparticles on the biochemical constituents of wheat crops infected with spot blotch disease. Silver nanoparticles (AgNPs) were synthesized using Mangifera indica leaf extract and their characterization was performed using UV-visible spectroscopy, SEM, XRD, and PSA. Characterization techniques confirm the presence of crystalline, spherical silver nanoparticles with an average size of 52 nm. The effect of green synthesized nanoparticles on antioxidative enzymes, e.g., Superoxide dismutase (SOD), Catalase (CAT), Glutathione Reductase (GR), Peroxidase (POX), and phytochemical precursor enzyme Phenylalanine Ammonia-Lyase (PAL), and on primary and secondary metabolites, e.g., reducing sugar and total phenol, in Bipolaris sorokiniana infected wheat crop were studied. Inoculation of fungal spores was conducted after 40 days of sowing. Subsequently, diseased plants were treated with silver nanoparticles at different concentrations. Elevation in all biochemical constituents was recorded under silver nanoparticle application. The treatment with a concentration of nanoparticles at 50 pp min diseased plants showed the highest resistance towards the pathogen. The efficacy of the green synthesized AgNPs as antibacterial agents was evaluated against multi drug resistant (MDR) bacteria comprising Gram-negative bacteria Escherichia coli (n = 6) and Klebsiella pneumoniae (n = 7) and Gram-positive bacteria Methicillin resistant Staphylococcus aureus (n = 2). The results show promising antibacterial activity with significant inhibition zones observed with the disc diffusion method, thus indicating green synthesized M. indica AgNPs as an active antibacterial agent against MDR pathogens.

Dry anaerobic co-digestion of food waste and cattle manure: Impact of total solids, substrate ratio and thermal pre treatment on methane yield and quality of biomanure.

The objective of the present study is to assess the impact of TS concentration, substrate mixing ratio (co digestion) and thermal pretreatment on biogas production, methane yield, VS reduction (%) and quality of biomanure through dry anaerobic digestion (DAD) of food waste (FW) and cattle manure (CM). Results divulged that the optimum methane yield and biomanure of 0.18 and 0.21 m3 CH4/(kg VS reduced) and 3.15 and 2.8 kg/kg waste was obtained from FW at TS of 25% and 30% at an HRT of 41 and 31 days respectively whereas it was 0.32 and 0.43 m3 CH4/(kg VS reduced) and 2.2 and 1.15 kg/kg waste from pretreated FW at an HRT of 16 and 20 days correspondingly. Improvement of methane from 62 to 81% was obtained due to thermal pretreatment. The highest nutrient recovery in terms of N, P, K was found to be 5.14, 2.6 and 3.2 respectively.