Infectious diseases account for 25% of the causes of death worldwide and this rate is expected to increase with the increasing rate of antibiotic resistance observed for many pathogens. Among the bacterial pathogens usually found in healthcare associated infections, Escherichia coli and Staphylococcus aureus are the most prevalent pathogens and, for the former, about 50% of the isolates are found to be methicillin resistant. Given the limited number of targets/pathways observed for the

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... of action for the existing antibiotics, the discovery of newer targets and their evaluation becomes an urgent and necessary task. Here we describe the structure-based identification of ticarcillin as a weak binder of the UDP-N-acetylglucosamine 2-epimerase (MnaA) from S. aureus. After a docking-based screening of existing drugs, ticarcillin was identified as a ligand in isothermal analysis of differential scanning fluorimetry data. An equilibrium molecular dynamics simulation confirmed the docking binding mode as a stable pose, with large contributions to the binding energy coming from interactions between Arg206 and Arg207 and the carboxylate groups in ticarcillin.