Herbal informatics and <i>in vitro</i> validation: Bio-prospection model to develop potent antibiotics against multi-drug resistant ESKAPE microorganisms

Abstract

ESKAPE refers to <i>Enterococcus</i> sp., <i>Staphylococcus</i> sp., <i>Klebsiella</i> sp., <i>Acinetobacter</i> sp., <i>Pseudomonas</i> sp., and <i>Enterobacter</i> sp. Nosocomial infections caused by ESKAPE pathogens have a high prevalence rate of 3.0-20.7% and an incidence rate of 5-10% globally, contributing to increased morbidity and mortality which has added noticeably to economic burden. Moreover, the chemotherapeutic modalities available for the management of ESKAPE pathogens confer serious hepato-renal toxicity. The rapid advancement of informatics approaches and literature surge led to the understanding of mechanism of action in more faster and specific manner. Some of the important virulence factors include adhesins, aerobactin system, hemolysin, capsular polysaccharides, biofilm formation, efflux pump, quorum sensing, beta-lactamase enzyme and various surface receptors that need to be targeted by using chemical modeling approaches. Six bacterial representative species of ESKAPE category were analyzed by targeting 05 virulence factors using combinatorial matrix approach. This <i>in silico</i> bioprospection analysis revealed 40 potential herbal leads amongst a database of 300 plants identified using classical bioprospection approach. The model has been validated at <i>in vitro</i> level against Carbapenem Resistant Enterobacteriaceae revealing 02 potent antibiotics (<i>Berberis</i> and <i>Camellia</i> sp.). The antibiotics were standardized using qualitative, quantitative and bioactivity descriptors.