Molecular Docking and Energetic Analysis of Deferoxamine in Uropathogenic Escherichia coli in an Experimental Model

Neurogenic bladder is a condition associated with impaired voiding, leading to urinary stasis and increased susceptibility to urinary tract infections, predominantly caused by Escherichia coli. In this context, bacterial iron acquisition systems represent attractive targets for alternative antimicrobial strategies. This study aimed to investigate the interactions of deferoxamine with E. coli iron acquisition proteins, combining an experimental model of neurogenic bladder with molecular analyses. The experimental model of neurogenic bladder was induced by complete spinal cord transection in rats, followed by urine collection by cystocentesis and microbiological characterization of uropathogens. Subsequently, molecular docking and energetic analyses were performed to evaluate the binding of deferoxamine and its Fe-DFO complex to the FhuE receptor of the ferric hydroxamate uptake pathway, with FhuA and FhuD prepared as correlated targets of the same pathway for structural context. The animals presented urinary retention and bacterial colonization, with E. coli identified as the pathogen. The results of the molecular docking revealed geometrically plausible accommodation of Fe-DFO within siderophore recognition pockets, involving residues associated with siderophore recognition and transport, as well as binding affinity scores consistent with weak-to-moderate structural complementarity compared to reference ligands. It is concluded that the neurogenic bladder model provides a biologically relevant framework for the study of urinary tract infections and that deferoxamine exhibits molecular interactions consistent with the ferric hydroxamate uptake system of E. coli. Because the present analysis was restricted to the Fhu pathway, these findings cannot be extrapolated to overall bacterial iron homeostasis, which involves multiple parallel acquisition systems. The current work is explicitly positioned as a proof-of-concept investigation; in vivo administration of DFO in the neurogenic bladder model, functional assays of iron uptake, transporter specificity experiments, and molecular dynamics analyses are identified as priority directions for future work.