Wang Tao, Associate Prof. of SUSTech Department of Biology, co-authored with Prof. Li Zigang in Peking University and published an article entitled Structure-based Identification of a Potent Inhibitor Targeting Stp1-mediated Virulence Regulation in Staphylococcus Aureus on Cell Chemical Biology, a Cell Press journal. The article introduces the crystal structure of staphylococcus aureus serine/ threonine phosphatase (Stp1) for the first time and discovers the inhibitor of targeting Stp1, revealing that Stp1 is a potential novel target resistant to staphylococcus aureus infection.

The abuse of antibiotics poses great selection pressure on bacteria and stimulates the emergence of antibiotic-resistant bacteria. In particular, methicillin-resistant staphylococcus aureus (MRSA), a kind of super bacteria with multi-drug resistance, has become the crux of clinical treatment, which urges the need for developing a new type of medicine resistant to bacterial infection. During the pathogenesis of MRSA, several kinds of virulent factors play a pivotal role in encroaching human tissues. Theoretically, targeting the bacterial growth of unnecessary virulent factors may decrease the possibility of bacterial infection, reduce the selection pressure of bacteria and suppress the appearance of antibiotic-resistant bacteria. It was discovered in previous research that Stp1 is an important virulent factor for staphylococcus aureas, so the inhibition of Stp1 is expected to decrease the chances of infection and avoid the emergence of antibiotic-resistant bacteria. The first inhibitor of Stp1, 5,5′-MDSA, was introduced in a research report in 2015 (ChemBioChem, 2015,16:1035-40).

In Wang Tao and Li Zigang’s article, researchers analyzed the crystal structure of Stp1 for the first time, and found out the binding of an unexpected fourth metal ion, which is also an unprecedented discovery. Then, through optimizing, screening and identifying three-dimensional space structural information, they pinpointed Aurintricarboxylic acid (ATA), an inhibitor with a higher survival rate. Experiments in vitro indicate that ATA can inhibit staphylococcus aureas to secrete relevant virulent factors through targeting Stp1. ATA doesn’t inhibit the in vitro growth of staphylococcus aureas, however, it can inhibit infection of staphylococcus aureas in mice. The research reveals that Stp1 is a feasible drug target resistant to the infection of staphylococcus aureas, which has blazed a new trail for the development of antibiotics replacement, especially the anti-virulence drugs resistant to bacterial infection.

Associate Prof. Wang Tao in Department of Biology at SUSTech and Prof. Li Zigang in Peking University are co-authors of this article. The research was supported by Ministry of Science and Technology, Natural Science Foundation of China (NSFC), Shenzhen Science and Technology Innovation Committee and Shenzhen “Peacock Plan”.

Link for the article: http://www.cell.com/cell-chemical-biology/fulltext/S2451-9456(16)30214-8