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Inhibition of sortase-mediated Staphylococcus aureus adhesion to fibronectin via fibronectin-binding protein by sortase inhibitors

  • Applied Microbial and Cell Physiology
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Abstract

The sortase enzymes are a family of Gram-positive transpeptidases responsible for anchoring surface protein virulence factors to the peptidoglycan cell wall layer. In Staphylococcus aureus, deletion of the sortase isoforms results in marked reduction in virulence and infection potential, making it an important antivirulence target. Recombinant sortase A (SrtA) and sortase B (SrtB) were incubated with peptide substrate containing either the LPETG or NPQTN motifs. (Z)-3-(2,5-dimethoxyphenyl)-2-(4-methoxyphenyl) acrylonitrile, β-sitosterol-3-O-glucopyranoside, berberine chloride, and psammaplin A1 showed potent inhibitory activity against SrtA and SrtB. These compounds also exhibited potent inhibitory activity against S. aureus cell adhesion to fibronectin. The fibronectin-binding activity data highlight the potential of these compounds for the treatment of S. aureus infections via inhibition of sortase activity.

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Acknowledgements

This work was supported by grant R01-2004-000-10429-0 from the Basic Research Program of the Korea Science & Engineering Foundation. M.N. Oh is recipient of fellowship from the Ministry of Education through the Brain Korea 21 Project. J.G. Kim was supported by the Korea Research Foundation Grant (KRF-2004-005-F00055).

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Correspondence to Ki-Bong Oh or Jongheon Shin.

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Oh, KB., Oh, MN., Kim, JG. et al. Inhibition of sortase-mediated Staphylococcus aureus adhesion to fibronectin via fibronectin-binding protein by sortase inhibitors. Appl Microbiol Biotechnol 70, 102–106 (2006). https://doi.org/10.1007/s00253-005-0040-8

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