Functional and Structural Properties of a Novel Protein and Virulence Factor (sHIP) in Streptococcus pyogenes

TY - JOUR

T1 - Functional and Structural Properties of a Novel Protein and Virulence Factor (sHIP) in Streptococcus pyogenes

AU - Wisniewska, Magdalena

AU - Happonen, Lotta

AU - Kahn, Fredrik

AU - Varjosalo, Markku

AU - Malmström, Lars

AU - Rosenberger, George

AU - Karlsson, Christofer

AU - Cazzamali, Giuseppe

AU - Pozdnyakova, Irina

AU - Frick, Inga-Maria

AU - Björck, Lars

AU - Streicher, Werner

AU - Malmström, Johan

AU - Wikström, Mats

N1 - Copyright © 2014, The American Society for Biochemistry and Molecular Biology.

PY - 2014/6/27

Y1 - 2014/6/27

N2 - Streptococcus pyogenes is a significant bacterial pathogen in the human population. The importance of virulence factors for the survival and colonization of S. pyogenes is well established, and many of these factors are exposed to the extracellular environment enabling bacterial interactions with the host. In the present study we quantitatively analyzed and compared S. pyogenes proteins in the growth medium of a strain that is virulent to mice, with a non-virulent strain. Particularly one of these proteins was present at significantly higher levels in stationary growth medium from the virulent strain. We determined the three-dimensional structure of the protein that showed a unique tetrameric organization composed of four helix-loop-helix motifs. Affinity pull-down mass spectrometry analysis in human plasma demonstrated that the protein interacts with histidine-rich glycoprotein (HRG), and the name sHIP (streptococcal Histidine-rich glycoprotein Interacting Protein) is therefore proposed. HRG has antibacterial activity, and when challenged by HRG, sHIP was found to rescue S. pyogenes bacteria. This and the finding that patients with invasive S. pyogenes infection respond with antibody production against sHIP, suggest a role for the protein in S. pyogenes pathogenesis.

AB - Streptococcus pyogenes is a significant bacterial pathogen in the human population. The importance of virulence factors for the survival and colonization of S. pyogenes is well established, and many of these factors are exposed to the extracellular environment enabling bacterial interactions with the host. In the present study we quantitatively analyzed and compared S. pyogenes proteins in the growth medium of a strain that is virulent to mice, with a non-virulent strain. Particularly one of these proteins was present at significantly higher levels in stationary growth medium from the virulent strain. We determined the three-dimensional structure of the protein that showed a unique tetrameric organization composed of four helix-loop-helix motifs. Affinity pull-down mass spectrometry analysis in human plasma demonstrated that the protein interacts with histidine-rich glycoprotein (HRG), and the name sHIP (streptococcal Histidine-rich glycoprotein Interacting Protein) is therefore proposed. HRG has antibacterial activity, and when challenged by HRG, sHIP was found to rescue S. pyogenes bacteria. This and the finding that patients with invasive S. pyogenes infection respond with antibody production against sHIP, suggest a role for the protein in S. pyogenes pathogenesis.

U2 - 10.1074/jbc.M114.565978

DO - 10.1074/jbc.M114.565978

M3 - Journal article

C2 - 24825900

SN - 0021-9258

VL - 289

SP - 18175

EP - 18188

JO - The Journal of Biological Chemistry

JF - The Journal of Biological Chemistry

ER -