Comparative genomics and e-pharmacophore search to identify novel therapeutic targets in the druggable genome of MDR Providencia stuartii

OBJECTIVES/BACKGROUND: Providencia species of the Enterobacteriaceae family is a frequent cause of hospitalised infections, primarily urinary tract infections. It has a major influence on patient morbidity, mortality, and therapy. They can cause pneumonia, meningitis, endocarditis, wound and bloodstream infections, thereby requiring serious attention for novel therapeutics identification at the preliminary stages of disease. METHODS: The AST (antimicrobial susceptibility test) of P. stuartii strains (n = 91) was followed by whole-genome sequencing using Oxford Nanopore MinION technology, comparative genomics (n = 19), resistome, and pharmacogenomics analyses. Pharmacokinetics and physicochemical characterisation of putative druggable targets and novel inhibitors were also evaluated. RESULTS: The reported genome is ∼4.43 Mb long, and the resistome has 30 different AMR genes. The pangenome revealed that it is open ('b' = 0.2314), and the core genome (n = 2611) revealed three potential targets that were screened against a peptidomimetic (n = 30,695) and a synthetic Isosteviol library (n = 37) for ensuing docking analyses. The top hit for each target was rendered to an MD (molecular dynamics) simulation. The stability of the apo- and complexes showed good indicators; RMSD (root mean square deviation) (proteins