Plant-derived phytochemicals as potential antibacterial agents for foodborne pathogen, Campylobacter jejuni targeting guaB-encoded IMPDH

Aim: This study aimed to identify novel plant-derived inhibitors targeting the guaB-encoded inosine monophosphate dehydrogenase (IMPDH, inosine 5’-monophosphate dehydrogenase) of the foodborne pathogen Campylobacter jejuni to address the rising global threat of multidrug-resistant infections. Method: The present research aimed to identify a novel candidate from medicinal plants using various drug discovery approaches, including network pharmacology, molecular docking, molecular dynamics (MD) simulations, and ADMET (absorption, distribution, metabolism, excretion, and toxicity) profiling to assess pharmacokinetic properties. Results: Molecular docking studies revealed that amaroswerin and eriocitrin had notable interactions with IMPDH, with docking scores of –8.612 and –8.488 kcal/mol, respectively. MD simulations for 200 ns showed that the amaroswerin-IMPDH complex remained stable until 99 ns, with a root mean square deviation (RMSD) of < 2.8 Å. However, this RMSD gradually increased and reached 4.5 Å by the end of the 200 ns trajectory. This indicates that complex underwent conformational adjustment. Amaroswerin showed a significant intestinal absorption rate of 49.29% and a notable permeability rate in Caco-2 cells. These data suggest it may be absorbed into the bloodstream more readily after oral administration. In terms of excretion, amaroswerin had a higher total clearance value of 0.465, indicating that it can be easily excreted from the body. ADMET analysis predicted moderate oral bioavailability and relatively favorable profiles across several toxicity endpoints, supporting amaroswerin as a promising candidate for further investigation. Nevertheless, these predictions are preliminary and require experimental validation of their pharmacokinetic and safety profiles. The organ toxicity and toxicity endpoints revealed that amaroswerin had higher inactive probability rates for hepatotoxicity (0.78), neurotoxicity (0.80), carcinogenicity (0.75), mutagenicity (0.66), and cytotoxicity (0.74), supporting its prioritization for further experimental evaluation. Conclusions: Based on the current computational findings, amaroswerin may be considered a promising lead compound for further investigation as an inhibitor of C. jejuni IMPDH. However, these findings do not establish antimicrobial efficacy or therapeutic suitability. Therefore, comprehensive in vitro and in vivo studies are required to experimentally validate IMPDH inhibition, antimicrobial activity, pharmacokinetic behavior, and safety before any consideration of clinical application.