Nanoparticle Fullerene (C60) demonstrated stable binding with antibacterial potential towards probable targets of drug resistant Salmonella typhi - a computational perspective and in vitro investigation.
Salmonella typhi, a Gram negative bacterium, has become multidrug resistant (MDR) to wide classes of antibacterials which necessitate an alarming precaution. This study focuses on the binding potential and therapeutic insight of Nano-Fullerene C60 towards virulent targets of Salmonella typhi by computational prediction and preliminary in vitro assays. The clinical isolates of Salmonella typhi were collected and antibiotic susceptibility profiles were assessed. The drug targets of pathogen were selected by rigorous literature survey and gene network analysis by various metabolic network resources. Based on this study, 20 targets were screened and the 3D structures of few drug targets were retrieved from PDB and others were computationally predicted. The structures of nanoleads such as Fullerene C60, ZnO and CuO were retrieved from drug databases. The binding potential of these nanoleads towards all selected targets were predicted by molecular docking. The best docked conformations were screened and concept was investigated by preliminary bioassays. This study revealed that most of the isolates of Salmonella typhi were found to be MDR (p < .05). The theoretical models of selected drug targets showed high stereochemical validity. The molecular docking studies suggested that Fullerene C60 showed better binding affinity towards the drug targets when compared to ZnO and CuO. The preliminary in vitro assays suggested that 100 μg/L Fullerene C60 posses significant inhibitory activities and absence of drug resistance to this nanoparticle. This study suggests that Fullerene C60 can be scaled up as probable lead molecules against the major drug targets of MDR Salmonella typhi.
a Department of Biotechnology Engineering , Dayananda Sagar Institutions, Visvesvaraya Technological University , Belagavi 560 078 , Karnataka , India.
Sinosh
S
Skariyachan
a Department of Biotechnology Engineering , Dayananda Sagar Institutions, Visvesvaraya Technological University , Belagavi 560 078 , Karnataka , India.
Asma
A
Parveen
a Department of Biotechnology Engineering , Dayananda Sagar Institutions, Visvesvaraya Technological University , Belagavi 560 078 , Karnataka , India.
Shruti
S
Garka
D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D052978:Disk Diffusion Antimicrobial Tests; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects* / Q000235:genetics; D037741:Fullerenes / Q000737:chemistry / Q000494:pharmacology*; D053263:Gene Regulatory Networks; D006801:Humans; D053858:Metabolic Networks and Pathways / Q000235:genetics; D062105:Molecular Docking Simulation; D053758:Nanoparticles / Q000737:chemistry*; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D017433:Protein Structure, Secondary; D012485:Salmonella typhi / Q000187:drug effects* / Q000254:growth & development / Q000302:isolation & purification / Q000378:metabolism; D040681:Structural Homology, Protein; D014435:Typhoid Fever / Q000382:microbiology
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D037741:Fullerenes; C069837:fullerene C60
Salmonella typhi; computational prediction; fullerene C60; gene network analysis; molecular docking Nanoleads; multi-drug resistant; therapeutic potential; virulent target proteins