Quest for antimicrobiol agent: from nanoparticle to computational biology (antimi crobial resistance element CFR as the target protein)

Abstract

Rapid emergence of superbugs at an unprecedented rate is posing great risk to human health. To address this issue, a diversified integrated approach of antibiotic development, scope of nanoparticles and in silico potentiators screening has been explored in this study. In this regard computation biology approach has been taken in consideration for identification of ligands that could be co-administered with the present-day PhLOPS antibiotics, especially chloramphenicol. The screening parameters ADMET was employed to screen ligands with drug-likeness. In addition, the ligand needed to be non-inhibitory to hMAT1A and Cyp450 3A4 due to their role in immunity and drug metabolism, hence molecular docking with these proteins were performed prior to final docking against the resistance element Cfr. The lead compound ZINC72320745 with inhibitory binding affinity against bacterial Cfr enzyme responsible for chloramphenicol clearance in bacteria has a furan scaffold that suggests the saprophytic nature of the Streptomyces sps. could be explored further with furfural supplementation in the media. However, in this research, tannic acid incorporated modified media was introduced to isolate robust Streptomyces, due to its polyphenolic stress inducing nature. Further, antimicrobials (antibiotic and biogenic nanoparticles) were synthesized and tested against standard pathogens after UV-Vis spectroscopy characterization of silver nanoparticles. The results showed the greater pathogen inhibition with silver nanoparticles than its secondary metabolite. Moreover, the FTIR analysis of the nanoparticle revealed presence of phenol, vinylic ether and imine or oxime group in extract, indicating responsible for its antimicrobial as well as reducing property. The isolate I53 has been found clade forming with Streptomyces rubiginosohelvolus strain 183DZ from the phylogenetic analysis suggesting relatedness. Keywords: Streptomycetes, antibiotics, Silver nanoparticle, Molecular docking, Cfr, RlmN, UV-Vis spectroscopy, FTIR