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Contribution of protein G-related alpha(2)-macroglobulin-binding protein to bacterial virulence in a mouse skin model of group a streptococcal infection

Toppel, AW; Rasmussen, Magnus LU ; Rohde, M; Medina, E and Chhatwal, GS (2003) In Journal of Infectious Diseases 187(11). p.1694-1703
Abstract
Protein G-related alpha(2)-macroglobulin-binding (GRAB) protein is a cell wall-attached determinant of group A streptococcus (GAS) that interacts with the human protease inhibitor a 2-macroglobulin (alpha(2)-M). Of 86 clinical isolates tested, 23% could bind a alpha(2)-M. However, all strains tested contained the grab gene. High levels of anti-GRAB antibodies were found in the serum of convalescent GAS-infected patients, a finding that indicates that this protein is expressed during the infection process. Among the alpha(2)-M-binding strains, 80% were skin isolates, and 20% were throat isolates, findings that suggest that the skin environment is a preferential site for expression of alpha(2)-M-binding activity. To test this possibility, we... (More)
Protein G-related alpha(2)-macroglobulin-binding (GRAB) protein is a cell wall-attached determinant of group A streptococcus (GAS) that interacts with the human protease inhibitor a 2-macroglobulin (alpha(2)-M). Of 86 clinical isolates tested, 23% could bind a alpha(2)-M. However, all strains tested contained the grab gene. High levels of anti-GRAB antibodies were found in the serum of convalescent GAS-infected patients, a finding that indicates that this protein is expressed during the infection process. Among the alpha(2)-M-binding strains, 80% were skin isolates, and 20% were throat isolates, findings that suggest that the skin environment is a preferential site for expression of alpha(2)-M-binding activity. To test this possibility, we determined the role of GRAB in a mouse model of GAS skin infection. The wild-type strain KTL3, which interacts with alpha(2)-M, showed high virulence. The isogenic mutant of KTL3, MR4, devoid of surface-bound GRAB, was attenuated in virulence, compared with the wildtype strain. Thus, mice infected with MR4 survived longer, developed smaller skin lesions, and exhibited lower levels of bacterial dissemination than did those infected with KTL3. These results emphasize the role of GRAB as a virulence factor of GAS. (Less)
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Contribution to journal
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published
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in
Journal of Infectious Diseases
volume
187
issue
11
pages
1694 - 1703
publisher
Oxford University Press
external identifiers
  • pmid:12751026
  • wos:000183279200003
ISSN
1537-6613
language
English
LU publication?
yes
id
6128c142-279d-449d-8318-940d8217ac73 (old id 309570)
alternative location
http://www.journals.uchicago.edu/JID/journal/issues/v187n11/30070/brief/30070.abstract.html
date added to LUP
2007-09-23 11:50:06
date last changed
2018-10-03 10:16:14
@article{6128c142-279d-449d-8318-940d8217ac73,
  abstract     = {Protein G-related alpha(2)-macroglobulin-binding (GRAB) protein is a cell wall-attached determinant of group A streptococcus (GAS) that interacts with the human protease inhibitor a 2-macroglobulin (alpha(2)-M). Of 86 clinical isolates tested, 23% could bind a alpha(2)-M. However, all strains tested contained the grab gene. High levels of anti-GRAB antibodies were found in the serum of convalescent GAS-infected patients, a finding that indicates that this protein is expressed during the infection process. Among the alpha(2)-M-binding strains, 80% were skin isolates, and 20% were throat isolates, findings that suggest that the skin environment is a preferential site for expression of alpha(2)-M-binding activity. To test this possibility, we determined the role of GRAB in a mouse model of GAS skin infection. The wild-type strain KTL3, which interacts with alpha(2)-M, showed high virulence. The isogenic mutant of KTL3, MR4, devoid of surface-bound GRAB, was attenuated in virulence, compared with the wildtype strain. Thus, mice infected with MR4 survived longer, developed smaller skin lesions, and exhibited lower levels of bacterial dissemination than did those infected with KTL3. These results emphasize the role of GRAB as a virulence factor of GAS.},
  author       = {Toppel, AW and Rasmussen, Magnus and Rohde, M and Medina, E and Chhatwal, GS},
  issn         = {1537-6613},
  language     = {eng},
  number       = {11},
  pages        = {1694--1703},
  publisher    = {Oxford University Press},
  series       = {Journal of Infectious Diseases},
  title        = {Contribution of protein G-related alpha(2)-macroglobulin-binding protein to bacterial virulence in a mouse skin model of group a streptococcal infection},
  volume       = {187},
  year         = {2003},
}