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; Mats Wikström

doi:10.1074/jbc.M114.565978

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, Mats Wikström

5 Citations (Scopus)

Abstract

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.

Original language	English
Journal	The Journal of Biological Chemistry
Volume	289
Pages (from-to)	18175-18188
ISSN	0021-9258
DOIs	https://doi.org/10.1074/jbc.M114.565978
Publication status	Published - 27 Jun 2014

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Wisniewska, M., Happonen, L., Kahn, F., Varjosalo, M., Malmström, L., Rosenberger, G., Karlsson, C., Cazzamali, G., Pozdnyakova, I., Frick, I-M., Björck, L., Streicher, W., Malmström, J., & Wikström, M. (2014). Functional and Structural Properties of a Novel Protein and Virulence Factor (sHIP) in Streptococcus pyogenes. The Journal of Biological Chemistry, 289, 18175-18188. https://doi.org/10.1074/jbc.M114.565978

Wisniewska, M, Happonen, L, Kahn, F, Varjosalo, M, Malmström, L, Rosenberger, G, Karlsson, C, Cazzamali, G, Pozdnyakova, I, Frick, I-M, Björck, L, Streicher, W, Malmström, J & Wikström, M 2014, 'Functional and Structural Properties of a Novel Protein and Virulence Factor (sHIP) in Streptococcus pyogenes', The Journal of Biological Chemistry, vol. 289, pp. 18175-18188. https://doi.org/10.1074/jbc.M114.565978

@article{a35ee857f73545348b9c83e33abb8599,

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

abstract = "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.",

author = "Magdalena Wisniewska and Lotta Happonen and Fredrik Kahn and Markku Varjosalo and Lars Malmstr{\"o}m and George Rosenberger and Christofer Karlsson and Giuseppe Cazzamali and Irina Pozdnyakova and Inga-Maria Frick and Lars Bj{\"o}rck and Werner Streicher and Johan Malmstr{\"o}m and Mats Wikstr{\"o}m",

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day = "27",

doi = "10.1074/jbc.M114.565978",

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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

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 - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

ER -

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

Abstract

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