Contribution of protein G-related alpha(2)-macroglobulin-binding protein to bacterial virulence in a mouse skin model of group a streptococcal infection
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/309570
- author
- Toppel, AW ; Rasmussen, Magnus LU ; Rohde, M ; Medina, E and Chhatwal, GS
- organization
- publishing date
- 2003
- type
- Contribution to journal
- publication status
- published
- subject
- 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
- 2016-04-01 16:15:55
- date last changed
- 2018-11-21 20:40:02
@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}},
url = {{http://www.journals.uchicago.edu/JID/journal/issues/v187n11/30070/brief/30070.abstract.html}},
volume = {{187}},
year = {{2003}},
}