Xuming Deng

Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University

The wide spread of drug resistance in bacterial pathogens coupled with the slowing of antibiotic discovery has become a grave challenge in public health. Treatment of infectious diseases by agents that specifically target pathogenic determinants has emerged as effective strategies in meeting the challenge without placing immediate life-or-death pressure on the target bacteria. According to the protein function, we have identified some natural compounds from traditional Chinese medicine as potential inhibitors of critical virulence factors, including hemolysin secreted by Staphylococcus aureus, Listeria monocytogenes and Streptococcus pneumoniae etc, sortase from gram positive pathogens and ribosome-inactivating proteins. These natural compounds could specially target the synthesis or function of the virulence factors without antibacterial activity. However, the pathogens virulence in both tissue culture and animal model infections was significantly inhibited in the presence of the natural compounds. Computational biology and structural biology assays were further employed to determined the mechanism of such inhibition. The direct binding of the inhibitors to the target protein would occupies the active site or inhibits/induces the oligomerization of the protein, thus abolishing the activity of the virulence factors and subsequently attenuating the pathogens virulence.  These results would partially elucidate the mechanism of natural compounds against bacterial infections and facilitate the development of anti-virulence drugs.