Metabolomic and molecular insights into adenosine triphosphate synthase inhibitors from Micromonospora sp. as novel antimicrobial agents against multidrug-resistant Gram-negative pathogens of enteric origin.

This article focuses on evaluating the antimicrobial potential of metabolic extracts from Micromonospora spp., particularly strain 65SH, against multidrug-resistant (MDR) Gram-negative bacteria of enteric origin. The study identified Micromonospora sp. 65SH, closely related to Micromonospora fluminis, as producing six bioactive compounds—melibiose, oligomycin A, queuine, heptelidic acid, diethyl phthalate, and 2′-deoxyguanosine—that inhibit bacterial ATP synthase and ATP-dependent topoisomerases, essential enzymes for bacterial proliferation. Using non-targeted metabolomics, molecular docking, and 16S rRNA gene sequencing, the research demonstrated significant antimicrobial activity of the strain’s extracts against clinical MDR isolates of Enterobacter aerogenes and Escherichia coli, with minimum inhibitory concentrations as low as 12.5 µg/ml. The findings highlight Micromonospora-derived metabolites as promising candidates for novel antibacterial agents targeting energy metabolism in resistant pathogens, with future work planned for structural elucidation and experimental validation.