Functional and Structural Properties of a Novel Protein and Virulence Factor (sHIP) in Streptococcus pyogenes
The group of Assoc. Prof. Mats Wikström at Novo Nordisk Foundation Center for Protein Research at University of Copenhagen has in collaboration with the groups of Assoc Prof. Johan Malmström and Prof. Lars Björck at Lund University, Sweden, identified a novel virulence factor in the pathogen Streptococcus pyogenes. Bacterial infections represent a major threat to humans, a threat that has been aggravated by the alarming and ongoing increase of antibiotic resistance recently discussed in a report by the World Health Organization (‘Antimicrobial resistance: global report on surveillance 2014’). Dr Keiji Fukuda, WHO’s Assistant Director-General for Health Security says, “Without urgent, coordinated action by many stakeholders, the world is headed for a post-antibiotic era, in which common infections and minor injuries which have been treatable for decades can once again kill,” S. pyogenes is one of the most significant bacterial pathogens (third most deadly) and a starting point for this study was the comparisons of the extracellular proteins in a high virulent strain (AP1) with a low virulent strain (SF370). We found that one protein in particular was present at significantly higher levels in the highly virulent strain. We determined the three-dimensional structure of this protein (the first protein structure determined at CPR) that showed a unique tetrameric organization.Three-dimensional structure for protein sHIP
Mass spectrometry analysis showed that the protein interacts with the antibacterial human protein histidine-rich glycoprotein (HRG) and the name sHIP (streptococcal Histidine-rich glycoprotein Interacting Protein) was therefore introduced. In addition, we could show that sHIP protects S. pyogenes from the antibacterial activity of HRG and that patients with invasive infection respond with increased antibody production against sHIP.
This collaborative project focusing on the identification of novel virulence factors in S. pyogenes has been published in the Journal of Biological Chemistry.
Functional and Structural Properties of a Novel Protein and Virulence Factor (sHIP) in Streptococcus pyogenes.
Magdalena Wisniewska, Lotta Happonen, Fredrik Kahn, Markku Varjosalo, Lars Malmström, George Rosenberger, Christofer Karlsson, Giuseppe Cazzamali, Irina Pozdnyakova, Inga-Maria Frick, Lars Björck, Werner Streicher, Johan Malmström, and Mats Wikström
Antimicrobial resistance: WHO Global Report on Surveillance 2014