In vitro and in silico prediction of bioactive compounds extracted from rhizosphere soil bacterium of Cassia fistula against Salmonella Typhi

The emerging risk of multidrug-resistant Salmonella Typhi emphasizes urgent focus towards the identification of novel antimicrobial compounds with new mechanisms of action. This article investigated the rhizosphere soil of Cassia fistula for bioactive bacteria that are rich in antimicrobial activities. Twelve bacterial isolates were collected and screened for antimicrobial activity; of these, VITBS7 showed the maximum activity. The strain VITBS7 was identified as Pseudomonas aeruginosa by 16S ribosomal DNA sequencing and phylogenetic analysis. Gas Chromatography-Mass Spectrometry (GC-MS) revealed six bioactive metabolites. Molecular docking of the metabolites extracted from the bacterial isolates against the S. Typhi penicillin-binding protein 1B (PBP1B), cross-validated with three independent scoring functions and a redocking control, showed that a coumarin carbonate derivative bound most strongly (-8.28 kcal/mol), exceeding the reference drug ampicillin (-7.77 kcal/mol); molecular dynamics simulations (3.0 µs aggregate) confirmed that this complex remained stable and specifically bound at the catalytic site over 300 ns. The majority of the compounds revealed desirable pharmacokinetic and bioavailability profiles from Absorption, Distribution, Metabolism, and Excretion (ADME) and drug-likeness studies. Further, the in vitro antibacterial tests demonstrated the potent activity of the metabolites against S. Typhi, comparable to those of reference antibiotics. The results obtained from the current study confirmed the antibacterial activity of metabolites derived from P. aeruginosa VITBS7, isolated from the rhizosphere soil of C. fistula , and possess a valuable lead for developing novel drugs against drug-resistant S. Typhi.