In silico molecular docking and in vitro antimicrobial efficacy of phytochemicals against multi-drug-resistant enteroaggregative Escherichia coli and non-typhoidal Salmonella spp.

Padikkamannil Abishad,Sukhadeo Baliram Barbuddhe,Sandeep Chaudhari,Nitin Vasantrao Kurkure,Varsha Unni,Pollumahanti Niveditha,Deepak Bhiwa Rawool,Jess Vergis

doi:10.1186/s13099-021-00443-3

Padikkamannil Abishad, Sukhadeo Baliram Barbuddhe + Show 6 more

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https://doi.org/10.1186/s13099-021-00443-3

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Abstract

BackgroundIn the wake of emergence of antimicrobial resistance, bioactive phytochemical compounds are proving to be important therapeutic agents. The present study envisaged in silico molecular docking as well as in vitro antimicrobial efficacy screening of identified phytochemical ligands to the dispersin (aap) and outer membrane osmoporin (OmpC) domains of enteroaggregative Escherichia coli (EAEC) and non-typhoidal Salmonella spp. (NTS), respectively.Materials and methodsThe evaluation of drug-likeness, molecular properties, and bioactivity of the identified phytocompounds (thymol, carvacrol, and cinnamaldehyde) was carried out using Swiss ADME, while Protox-II and StopTox servers were used to identify its toxicity. The in silico molecular docking of the phytochemical ligands with the protein motifs of dispersin (PDB ID: 2jvu) and outer membrane osmoporin (PDB ID: 3uu2) were carried out using AutoDock v.4.20. Further, the antimicrobial efficacy of these compounds against multi-drug resistant EAEC and NTS strains was determined by estimating the minimum inhibitory concentrations and minimum bactericidal concentrations. Subsequently, these phytochemicals were subjected to their safety (sheep and human erythrocytic haemolysis) as well as stability (cationic salts, and pH) assays.ResultsAll the three identified phytochemicals ligands were found to be zero violators of Lipinski’s rule of five and exhibited drug-likeness. The compounds tested were categorized as toxicity class-4 by Protox-II and were found to be non- cardiotoxic by StopTox. The docking studies employing 3D model of dispersin and ompC motifs with the identified phytochemical ligands exhibited good binding affinity. The identified phytochemical compounds were observed to be comparatively stable at different conditions (cationic salts, and pH); however, a concentration-dependent increase in the haemolytic assay was observed against sheep as well as human erythrocytes.ConclusionsIn silico molecular docking studies provided useful insights to understand the interaction of phytochemical ligands with protein motifs of pathogen and should be used routinely before the wet screening of any phytochemicals for their antibacterial, stability, and safety aspects.

Highlights

In the wake of emergence of antimicrobial resistance, bioactive phytochemical compounds are proving to be important therapeutic agents
The identified phytochemical compounds were observed to be comparatively stable at different conditions; a concentration-dependent increase in the haemolytic assay was observed against sheep as well as human erythrocytes
In silico molecular docking studies provided useful insights to understand the interaction of phytochemical ligands with protein motifs of pathogen and should be used routinely before the wet screening of any phytochemicals for their antibacterial, stability, and safety aspects

Summary

Introduction

In the wake of emergence of antimicrobial resistance, bioactive phytochemical compounds are proving to be important therapeutic agents. Contamination of foods can lead to food-borne illnesses that can occur at any point of production, processing, distribution, and consumption. This emerging public health problem causes considerable obstruction to socio-economic development as well as contributes significantly to the global burden of disability, morbidity, and mortality. Non-typhoidal Salmonella (NTS) serovars and diarrhoeagenic E. coli (DEC) pathotypes constitute the leading causes of gastrointestinal infections worldwide [4, 5]. It has been estimated that the mortality rate by way of AMR would increase to the tune of 10 million by 2050, which would further decrease the gross domestic product (GDP) by 3.50 %, resulting in an overall global economic loss of nearly USD 100 trillion [11]. The focus has primarily been shifted towards alternative therapeutic strategies to counter the menace of AMR, apart from the routinely employed antibiotics [13]

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