Gallic Acid: A Potent Metabolite Targeting Shikimate Kinase in Acinetobacter baumannii

<b>Background/Objectives:</b><i>Acinetobacter baumannii</i> is a highly multidrug-resistant pathogen resistant to almost all classes of antibiotics; new therapeutic strategies against this infectious agent are urgently needed. Shikimate kinase is an enzyme belonging to the shikimate pathway and has become a potential target for drug development. This work describes the search for Food and Drug Administration (FDA)-approved drugs and natural compounds, including gallic acid, that could be repurposed as selective shikimate kinase inhibitors by integrated computational and experimental approaches. <b>Methods:</b> Approaches to drug design using structure-based and ligand-based methodology, in-silico screening, molecular docking, and molecular dynamics for the study of both binding affinity and stability. Experimental Validation Determination of minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) on <i>Acinetobacter baumannii</i> and <i>Enterococcus faecalis</i>. <b>Results/Conclusions:</b> Among them, gallic acid, obtained from plants, proved to be the most promising compound that showed sufficient binding with shikimate kinase through computational studies. Gallic acid showed very good activity against <i>Acinetobacter baumannii</i> and <i>Enterococcus faecalis</i> in the MIC and MBC assay, respectively. Gallic acid exhibited better activity against <i>Acinetobacter baumannii</i> due to the overexpression of shikimate kinase. Gallic acid has emerged as a potential therapeutic candidate drug against <i>A. baumannii</i> infection and, therefore, as a strategy against the appearance of multidrug-resistant microorganisms. This study not only identifies a novel repurposing opportunity for gallic acid but also provides a comprehensive computational and experimental framework for accelerating antimicrobial drug discovery against multidrug-resistant pathogens.