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© Mélanie Falord, Tarek Msadek, Jean-Marc Panaud
Staphylococcus aureus "golden staph" in scanning electron microscopy.
Publication : Proceedings of the National Academy of Sciences of the United States of America

Antiinfective therapy with a small molecule inhibitor of Staphylococcus aureus sortase

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Proceedings of the National Academy of Sciences of the United States of America - 02 Sep 2014

Zhang J, Liu H, Zhu K, Gong S, Dramsi S, Wang YT, Li J, Chen F, Zhang R, Zhou L, Lan L, Jiang H, Schneewind O, Luo C, Yang CG

Link to Pubmed [PMID] – 25197057

Proc. Natl. Acad. Sci. U.S.A. 2014 Sep;111(37):13517-22

Methicillin-resistant Staphylococcus aureus (MRSA) is the most frequent cause of hospital-acquired infection, which manifests as surgical site infections, bacteremia, and sepsis. Due to drug-resistance, prophylaxis of MRSA infection with antibiotics frequently fails or incites nosocomial diseases such as Clostridium difficile infection. Sortase A is a transpeptidase that anchors surface proteins in the envelope of S. aureus, and sortase mutants are unable to cause bacteremia or sepsis in mice. Here we used virtual screening and optimization of inhibitor structure to identify 3-(4-pyridinyl)-6-(2-sodiumsulfonatephenyl)[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole and related compounds, which block sortase activity in vitro and in vivo. Sortase inhibitors do not affect in vitro staphylococcal growth yet protect mice against lethal S. aureus bacteremia. Thus, sortase inhibitors may be useful as antiinfective therapy to prevent hospital-acquired S. aureus infection in high-risk patients without the side effects of antibiotics.

http://www.ncbi.nlm.nih.gov/pubmed/25197057