Bleomycin targets HisG, inhibits multidrug-resistant Acinetobacter baumannii growth in vitro.

Acinetobacter baumannii has emerged as a critical global pathogen, particularly in hospital settings, due to its escalating antibiotic resistance and limited therapeutic options. Conventional treatments are increasingly ineffective, necessitating novel strategies. The histidine biosynthesis pathway, absent in humans but vital for bacterial survival, presents a promising drug target. This study specifically focuses on ATP phosphoribosyltransferase (HisG), the enzyme catalyzing the first committed step in this essential bacterial pathway.

Researchers investigated Bleomycin's potential to inhibit A. baumannii HisG. Initial virtual screening identified Bleomycin as a top candidate based on favorable docking scores. Molecular interaction analysis then detailed strong binding within the enzyme's active site. To validate these computational predictions, surface plasmon resonance (SPR) was used to assess binding kinetics of Bleomycin to recombinant HisG. Finally, in vitro antibacterial assays were conducted to determine the minimum inhibitory concentration (MIC) and time-dependent growth effects of Bleomycin on A. baumannii.

Computational analysis revealed Bleomycin strongly binds within the HisG active site, interacting with key catalytic residues. SPR validation confirmed this interaction, showing a dissociation constant (KD) of 270 nM, indicating a moderate to strong affinity between Bleomycin and recombinant HisG. In in vitro antibacterial assays, Bleomycin significantly inhibited A. baumannii growth. > The minimum inhibitory concentration (MIC) for Bleomycin against A. baumannii was determined to be 7.8125 µg/mL. Time-dependent growth studies further demonstrated strong bacteriostatic activity of Bleomycin at and above MIC concentrations, effectively suppressing bacterial proliferation. These findings collectively suggest Bleomycin directly targets HisG and exerts potent antibacterial effects.