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Functional dissection of Streptococcus pyogenes M5 protein: the hypervariable region is essential for virulence.

Waldemarsson, Johan LU ; Stålhammar-Carlemalm, Margaretha LU ; Sandin, Charlotta LU ; Castellino, Francis J and Lindahl, Gunnar LU (2009) In PLoS ONE 4(10).
Abstract
The surface-localized M protein of Streptococcus pyogenes is a major virulence factor that inhibits phagocytosis, as determined ex vivo. Because little is known about the role of M protein in vivo we analyzed the contribution of different M protein regions to virulence, using the fibrinogen (Fg)-binding M5 protein and a mouse model of acute invasive infection. This model was suitable, because M5 is required for mouse virulence and binds mouse and human Fg equally well, as shown here. Mixed infection experiments with wild type bacteria demonstrated that mutants lacking the N-terminal hypervariable region (HVR) or the Fg-binding B-repeat region were strongly attenuated, while a mutant lacking the conserved C-repeats was only slightly... (More)
The surface-localized M protein of Streptococcus pyogenes is a major virulence factor that inhibits phagocytosis, as determined ex vivo. Because little is known about the role of M protein in vivo we analyzed the contribution of different M protein regions to virulence, using the fibrinogen (Fg)-binding M5 protein and a mouse model of acute invasive infection. This model was suitable, because M5 is required for mouse virulence and binds mouse and human Fg equally well, as shown here. Mixed infection experiments with wild type bacteria demonstrated that mutants lacking the N-terminal hypervariable region (HVR) or the Fg-binding B-repeat region were strongly attenuated, while a mutant lacking the conserved C-repeats was only slightly attenuated. Because the HVR of M5 is not required for phagocytosis resistance, our data imply that this HVR plays a major but unknown role during acute infection. The B-repeat region is required for phagocytosis resistance and specifically binds Fg, suggesting that it promotes virulence by binding Fg. However, B-repeat mutants were attenuated even in Fg-deficient mice, implying that the B-repeats may have a second function, in addition to Fg-binding. These data demonstrate that two distinct M5 regions, including the HVR, are essential to virulence during the early stages of an infection. In particular, our data provide the first in vivo evidence that the HVR of an M protein plays a major role in virulence, focusing interest on the molecular role of this region. (Less)
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organization
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Contribution to journal
publication status
published
subject
in
PLoS ONE
volume
4
issue
10
publisher
Public Library of Science
external identifiers
  • wos:000270354200006
  • pmid:19794915
  • scopus:70349696165
ISSN
1932-6203
DOI
10.1371/journal.pone.0007279
language
English
LU publication?
yes
id
cca2f9ea-a57e-4642-ac5b-99faf34c173d (old id 1500850)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19794915?dopt=Abstract
date added to LUP
2009-11-04 11:01:18
date last changed
2017-01-01 07:54:05
@article{cca2f9ea-a57e-4642-ac5b-99faf34c173d,
  abstract     = {The surface-localized M protein of Streptococcus pyogenes is a major virulence factor that inhibits phagocytosis, as determined ex vivo. Because little is known about the role of M protein in vivo we analyzed the contribution of different M protein regions to virulence, using the fibrinogen (Fg)-binding M5 protein and a mouse model of acute invasive infection. This model was suitable, because M5 is required for mouse virulence and binds mouse and human Fg equally well, as shown here. Mixed infection experiments with wild type bacteria demonstrated that mutants lacking the N-terminal hypervariable region (HVR) or the Fg-binding B-repeat region were strongly attenuated, while a mutant lacking the conserved C-repeats was only slightly attenuated. Because the HVR of M5 is not required for phagocytosis resistance, our data imply that this HVR plays a major but unknown role during acute infection. The B-repeat region is required for phagocytosis resistance and specifically binds Fg, suggesting that it promotes virulence by binding Fg. However, B-repeat mutants were attenuated even in Fg-deficient mice, implying that the B-repeats may have a second function, in addition to Fg-binding. These data demonstrate that two distinct M5 regions, including the HVR, are essential to virulence during the early stages of an infection. In particular, our data provide the first in vivo evidence that the HVR of an M protein plays a major role in virulence, focusing interest on the molecular role of this region.},
  articleno    = {e7279},
  author       = {Waldemarsson, Johan and Stålhammar-Carlemalm, Margaretha and Sandin, Charlotta and Castellino, Francis J and Lindahl, Gunnar},
  issn         = {1932-6203},
  language     = {eng},
  number       = {10},
  publisher    = {Public Library of Science},
  series       = {PLoS ONE},
  title        = {Functional dissection of Streptococcus pyogenes M5 protein: the hypervariable region is essential for virulence.},
  url          = {http://dx.doi.org/10.1371/journal.pone.0007279},
  volume       = {4},
  year         = {2009},
}