Dataset Information

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

ABSTRACT:

Background

In 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 methods

The 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.

Results

All 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.

Conclusions

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.

SUBMITTER: Abishad P

PROVIDER: S-EPMC8286599 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:The World Health Organisation has defined "highest priority critically important antimicrobials" (CIAs) as those requiring the greatest control during food production. Evidence demonstrating that restricted antimicrobial usage prevents the emergence of resistance to CIA's amongst pathogenic and commensal organisms on a production system-wide scale would strengthen international efforts to control antimicrobial resistance (AMR). Therefore, in a designed survey of all major chicken-meat producers in Australia, we investigated the phenotypic AMR of E. coli (n = 206) and Salmonella (n = 53) from caecal samples of chickens at slaughter (n = 200). A large proportion of E. coli isolates (63.1%) were susceptible to all tested antimicrobials. With regards to CIA resistance, only two E.coli isolates demonstrated resistance to fluoroquinolones, attributed to mutations in the quinolone resistance-determining regions of gyrA. Antimicrobial resistance was observed for trimethoprim/sulfamethoxazole (8.7%), streptomycin (9.7%), ampicillin (14.1%), tetracycline (19.4%) and cefoxitin (0.5%). All Salmonella isolates were susceptible to ceftiofur, chloramphenicol, ciprofloxacin, colistin, florfenicol, gentamicin and tetracycline. A low frequency of Salmonella isolates exhibited resistance to streptomycin (1.9%), ampicillin (3.8%), and cefoxitin (11.3%). AMR was only observed among Salmonella Sofia serovars. None of the Salmonella isolates exhibited a multi-class-resistant phenotype. Whole genome sequencing did not identify any known resistance mechanisms for the Salmonella isolates demonstrating resistance to cefoxitin. The results provide strong evidence that resistance to highest priority CIA's is absent in commensal E. coli and Salmonella isolated from Australian meat chickens, and demonstrates low levels of resistance to compounds with less critical ratings such as cefoxitin, trimethoprim/sulfamethoxazole, and tetracycline. Apart from regulated exclusion of CIAs from most aspects of livestock production, vaccination against key bacterial pathogens and stringent biosecurity are likely to have contributed to the favorable AMR status of the Australian chicken meat industry. Nevertheless, industry and government need to proactively monitor AMR and antimicrobial stewardship practices to ensure the long-term protection of both animal and human health.

Project description:BackgroundSalmonella spp. and pathogenic strains of Escherichia coli are among the major foodborne zoonotic pathogens. These bacterial pathogens cause human illnesses characterized by hemorrhagic colitis, vomiting, nausea, and other agent-related symptoms. The increasing occurrence of antimicrobial resistance in these pathogens is also a serious public health concern globally. Regular surveillance of phenotypes and genotypes of Salmonella spp. and Escherichia coli from animal-derived foods is necessary for effective reduction and control of these foodborne pathogens. This study was conducted to assess the occurrence, antimicrobial resistance, virulence genes and genetic diversity of Salmonella spp. and E. coli isolates from fresh Nile tilapia obtained from retail markets in Nairobi, Kenya.MethodsA total of 68 fresh Nile tilapia fish samples were collected from retail markets and used for isolation of Salmonella spp. and E. coli. Antimicrobial susceptibilities of the isolates weretested by Kirby-Bauer agar disc diffusion method. According to the antimicrobial resistance profiles, the multi-drug resistant isolates were identified by 16 S rRNA sequencing and phylogenetic analysis using the Bayesian inference method. The MDR Salmonella spp. and E. coli isolates were subjected to PCR-based screening for the detection virulence and antibiotic resistance genes.ResultsThe prevalence of contamination of the fish samples with Salmonella spp. and E.coli was 26.47% and 35.29% respectively. Overall phenotypic resistance among the Salmonella spp. ranged from 5.5% for ceftazidime, chloramphenicol, meropenem, nitrofurantoin and streptomycin and 22.2% for penicillin-G. For E. coli phenotypic resistance ranged from 4.2% for ceftazidime and chloramphenicol and 25% for rifampicin. Multi-drug resistance was observed in three Salmonella spp. and two E. coli isolates. Results of 16 S rRNA sequences, sequence alignment and phylogenic trees confirmed the identified MDR isolates as S. typhymurium WES-09, S. typhymurium MAK-22, S. typhimurium EMB-32 and E. coli MAK-26 and E. coli LAN-35. The presence of antibiotic-resistance genes belonging to β-lactamases, tetracycline, sulfonamide, trimethoprim and aminoglycosides-resistant genes were detected in all the identified MDR isolates.ConclusionsThe findings from this study indicate that Nile tilapia (Oreochromis niloticus) sold in retail markets can acts as reservoirs of Salmonella spp. and E. coli pathogens linked to human disease, some of which were multidrug resistance to critically important antimicrobials. Both microorganisms are of zoonotic significance and represent a significant public health risk to the society.