Investigation on Quorum Sensing Modulatory Potential of Certain Plant Products Against Selected Pathogenic Bacteria

Abstract

Anti-Microbial Resistance (AMR) refers to the ability of microbes to become resistant to antimicrobial drugs. The development of bacterial resistance to antibiotics, is increasing rapidly around the world. Several factors that play a role include sanitation, health-care facilities, standards of infection control, etc. Thus, AMR is a biological phenomenon but, driven by many socio-economic conditions. The need for selection of resistance by an organism arises from its exposure to life-threatening circumstances on exposure to antimicrobials. And hence, we here seek to solve the problem of AMR by targeting the pathogenicity of the organism and not its survival. This anti-infective strategy employs the use of quorum sensing modulatory (QSM) compounds derived from plants (phytocompounds). A total of 15 phytocompounds present in pomegranate peel extract namely, Acacetin, Benzoic acid, Catechin, Chlorogenic acid, Cinnamic acid, Coumaric acid, Ellagic acid, Ferulic acid, Gallic acid, Genistein, Kaempferol, Luteolin, Pedunculagin, Quercetin and Rutin were tested in silico for their possible QSM activity against receptors of quorum sensing system present in Chromobacterium violaceum, Pseudomonas aeruginosa and Staphylococcus aureus. From in silico screening, 4 compounds – Chlorogenic acid, Cinnamic acid, Coumaric acid and Ferulic acid were selected multiple criteria such as binding affinity, no. of hydrogen bonds involved in the binding, overlapping residues, literature review, availability of the compounds, etc. for in vitro primary screening against C. violaceum, P. aeruginosa, S. aureus and Serratia marcescens. Three of the four microbes have their place in the WHO priority pathogens list for R&D of new antibiotics (2017) and are involved primarily in wound infections and majority of the nosocomial infections. Primary screening in vitro proved Chlorogenic acid at concentration of 25μg/ml to 75 μg/ml to be a promising QSM compound against P. aeruginosa and was thus tested once for in vivo efficacy in an animal model - Caenorhabditis elegans. Chlorogenic acid 8 could not yield encouraging results in vivo and thus refinement of the procedures executed is required for a further successful endeavour. Additionally, in vitro QSM activity of commercially available Curcumin and Pomegranate peel extracts was evaluated against all the 4 previously mentioned pathogenic microbes and encouraging results were obtained in both the cases. Thereby, proving both to be promising QSM compounds against these pathogens, if the activity is confirmed in vivo.