Amphotericin B (AMPH) is an anti-fungal drug and this study, for the first time as best of our knowledge, reports the repurposing of the Amphotericin B. The drug was found to show significant antibacterial potential revealed by antimicrobial screening, molecular docking, and mode of action analysis targeting Penicillin Binding Protein 2a (PBP 2a protein) which is target of β-lactam drugs and is involved in cell wall synthesis. Mode of action analysis showed the drug to have hydrophobic and hydrophilic interactions with both C-terminal, trans-peptidase and non-penicillin binding domain of the protein. Additionally, to evaluate the impact of ligand binding on the protein's conformational dynamics, molecular dynamics (MD) simulations were used. Comparative Dynamical flexibility (RMSF) and Dynamics Cross Correlation (DCCM) followed by MD simulations revealed the complex formation significantly effecting structural dynamics of the enzyme significantly in the non-penicillin binding domain (327–668) and slightly in trans peptidase domain. Radius of gyration assessment further showed ligand binding also decreasing over all compactness of protein. Secondary structure analysis indicated the complex formation changing the conformational integrity in non-penicillin binding domain. Hydrogen bond analysis and MMPBSA, free energy of calculations followed by MD simulations, also complemented the antimicrobial and molecular docking revelations suggesting Amphotericin B to have substantial antibacterial potential.

Bacteriocins are gaining immense importance in therapeutics since they show significant antibacterial potential. This study reports the bacteriocin KAE01 from Enterococcus faecium, along with its characterization, molecular modeling, and antibacterial potency, by targeting the matrix protein of Pseudomonas aeruginosa. The bacteriocin was purified by using ammonium sulfate precipitation and fast protein liquid chromatography (FPLC), and its molecular weight was estimated as 55 kDa by means of SDS-PAGE. The bacteriocin was found to show stability in a wide range of pH values (2.0–10.0) and temperatures (100 °C for 1 h and 121 °C for 15 min). Antimicrobial screening of the purified peptide against different strains of P. aeruginosa showed its significant antibacterial potential. Scanning electron microscopy of bacteriocin-induced bacterial cultures revealed significant changes in the cellular morphology of the pathogens. In silico molecular modeling of KAE01, followed by molecular docking of the matrix protein (qSA) of P. aeruginosa and KAE01, supported the antibacterial potency and SEM findings of this study.

Background: Multi drug-resistance pose a great threat to public health and are responsible for various life-threatening ailments. There is a crucial need to control the outbreaks by finding alternatives to the conventional drugs available. Over the last few years, the usage of probiotics, including Lactobacillus spp. and their bacteriocins has gained much attention to ward off various diseases. Methods: This study was focused on characterizing bacteriocins extracted from Lactobacillus spp. and assessing their antagonistic effect against multi-drug resistant bacteria. Fifteen Lactobacillus spp. were isolated and identified from Pakistani dairy and fermented products (raw milk, cheese, butter milk, pickle and yoghurt). All the isolates were preliminarily screened by the antagonism method of agar well diffusion method, and the bacteriocins were isolated by ammonium sulphate method. Afterwards, to evaluate the release of bacteriocin in liquid medium, the Cell-Free Supernatant Fluid (CFSF) of the best producer strains were tested by agar well diffusion assay. To assess the thermostability of the bacteriocins, they were subjected to temperatures of 40ᴼC, 60ᴼC, 80ᴼC and 100ᴼC. Results: The study allowed the selection of five bacteriocin producing strains Lactobacillus acidophilus KAL1, Lactobacillus casei KAL3, Lactobacillus plantarum KAL5, Lactobacillus reuteri KAL6 and Lactobacillus spp. delbrukei KAL7, endowed with the strongest and broadest inhibitory ability against both Gram-positive (Methicillin Resistant Staphylococcus aureus) and Gram-negative (Pseudomonas aeruginosa) bacteria. Bacteriocins isolated were significantly thermostable with activity at 80ᴼC (30, 20 min) respectively. Moreover, all the bacteriocins were considerably stable at a range of pH (4–8) but all the activity was eliminated against proteolytic enzyme Proteinase K. Conclusion: From this study, it was concluded that bacteriocin extracts from five isolated Lactobacillus spp. can be considered a preferable candidate against multi-drug resistant pathogens. These partially purified bacteriocins should be further processed to attain purified product that could be useful for further studies for the control of pathogens, food spoilage and preservation purposes.

Editorial: Omics and its integration: a systems biology approach to understanding plant physiology