Structural highlights
Publication Abstract from PubMedThe critical role of sortase A in gram-positive bacterial pathogenicity makes this protein a good potential target for antimicrobial therapy. In this study, we report for the first time the crystal structure of Listeria monocytogenes sortase A and identify the active sites that mediate its transpeptidase activity. We also used a sortase A (SrtA) enzyme activity inhibition assay, simulation, and isothermal titration calorimetry analysis to discover that chalcone, an agent with little anti-L. monocytogenes activity, could significantly inhibit sortase A activity with an IC50 of 28.41 +/- 5.34 muM by occupying the active site of SrtA. The addition of chalcone to a co-culture of L. monocytogenes and Caco-2 cells significantly inhibited bacterial entry into the cells and L. monocytogenes-mediated cytotoxicity. Additionally, chalcone treatment decreased the mortality of infected mice, the bacterial burden in target organs, and the pathological damage to L. monocytogenes-infected mice. In conclusion, these findings suggest that chalcone is a promising candidate for the development of treatment against L. monocytogenes infection. Inhibition of sortase A by chalcone prevents Listeria monocytogenes infection.,Li H, Chen Y, Zhang B, Niu X, Song M, Luo Z, Lu G, Liu B, Zhao X, Wang J, Deng X Biochem Pharmacol. 2016 Apr 15;106:19-29. doi: 10.1016/j.bcp.2016.01.018. Epub, 2016 Jan 28. PMID:26826492[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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