Covalent sortase A inhibitor ML346 prevents Staphylococcus aureus infection of Galleria mellonella.

ABSTRACT: The housekeeping sortase A (SrtA), a membrane-associated cysteine transpeptidase, is responsible for anchoring surface proteins to the cell wall peptidoglycan in Gram-positive bacteria. This process is essential for the regulation of bacterial virulence and pathogenicity. Therefore, SrtA is considered to be an ideal target for antivirulence therapy. In this study, we report that ML346, a compound with a barbituric acid and cinnamaldehyde scaffold, functions as an irreversible inhibitor of Staphylococcus aureus SrtA (SaSrtA) and Streptococcus pyogenes SrtA (SpSrtA) in vitro at low micromolar concentrations. According to our X-ray crystal structure of the SpSrtA_ΔN81/ML346 complex (Protein Data Bank ID: 7V6K), ML346 covalently modifies the

SUBMITTER: Guan XN 

PROVIDER: S-EPMC8864484 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature