Screening of Putative Therapeutic Candidates in Superbug (Staphylococcus Aureus): A Systematic in Silico Approach

Abstract

Objective: Staphylococcus aureus, a superbug and antibiotic resistant pathogen, is one of the most infection causing organism, ranging from skin allergies to severe lethal conditions. The prolonged use of different antibiotics and lack of optimal treatment over the antibiotic resistant species, led to the identification of new, better and promising therapeutic candidates.Methods: A systematic in silico filtration process was employed, which includes subtractive channels and reverse vaccinology techniques.Results: Here, we report 12 possible drug targets and two vaccine candidates based on essentiality, non-human homolog, virulent and localization, commonly in all the strains. Further characterization studies such as pathway analysis, chokepoint and structure prediction revealed, two proteins as the best drug targets one being novel and the other druggable. Only one protein has shown the characteristic feature of vaccine candidate, having antigenic property and an IgG binding domain. Conclusion:Two best drug targets were commonly identified in all the strains of S. aureus namely UDP-N-acetylmuramoyl-L-alanyl-D-glutamate--L-lysine ligase (MurE) and cell division protein FtsA, whereas the best common vaccine candidate includes Peptidoglycan binding protein. The therapeutic candidates reported in the present study might facilitate screening of new and better antimicrobial compounds, for an optimal treatment of S. aureus infections.

Preclinical Studies and Clinical Trials in Determination of Safety and Efficacy of Meningococcal Vaccines: Present Scenario

“…Parameters such as seroconversion rates, geometric mean antibody titers [30] are characterized using animal models in vaccine development. Animal studies are crucial in verifying the outcomes of the in silico mathematical tools such as differential equation (DE) modeling, agent-based modeling, and systematic in silico screening approach with different filtering phases [30,40]. Animal models are indispensable for assessment of pharmacodynamic endpoints associated with vaccines.…”

Structure-Based Discovery of Inhibitors Against MurE in Methicillin-Resistant Staphylococcus Aureus

“…One of the identified microbial pathogen that has remarkably developed drug resistance is Staphylococcus aureus, a gram-positive and facultative anaerobe. It is one of the leading cause of infection, ranging from minor skin allergies and simple boils to severe lethal conditions such as necrotizing pneumonia and toxic shock syndrome 4,5 .…”

“…Methicillin, like other β-lactam antibiotics such as oxacillin, penicillin, and cephalosporins, was commonly used to treat S. aureus infections 4 . Its mechanism involves competitive inhibition of the transpeptidase enzyme used by bacteria to crosslink the D-alanyl-alanine peptide, which is vital for peptidoglycan synthesis 6 .…”