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Updated: Jan 20, 2026

Development and Assessment of Intracellular Infection Models for Staphylococcus aureus
Published on: January 17, 2025
Discovery and development of substituted thiadiazoles as inhibitors of Staphylococcus aureus Sortase A
Patrick M Wehrli1, Ivana Uzelac2, Thomas Olsson2
1Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, Sweden; Centre for Antibiotic Resistance Research (CARe) at University of Gothenburg, Gothenburg, Sweden.
Abstract:
High-throughput screening of small-molecule libraries has led to the identification of thiadiazoles as a new class of inhibitors against Staphylococcus aureus sortase A (SrtA). N-(5-((4-nitrobenzyl)thio)-1,3,4-thiadiazol-2-yl)nicotinamide (IC50 = 3.8 µM) was identified as a potent inhibitor of SrtA after synthetic modification of hit compounds. Additional ligands developed in this study displayed affinities in the low micromolar range without affecting bacterial growth in vitro. The study also suggest a new mode of action through covalent binding to the active site cysteine.
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