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SclA, a novel collagen-like surface protein of Streptococcus pyogenes

Rasmussen, Magnus LU ; Eden, A and Björck, Lars LU (2000) In Infection and Immunity 68(11). p.6370-6377
Abstract
Surface proteins of Streptococcus pyogenes are important virulence factors. Here we describe a novel collagen-like surface protein, designated SclA (streptococcal collagen-like surface protein). The sclA gene was identified in silico using the Streptococcal Genome Sequencing Project with the recently identified protein GRAB as the probe. SclA has a signal sequence and a cell wall attachment region containing the prototypic LPXTGX motif. The surface-exposed part of SclA contains a unique NH(2)-terminal domain of 73 amino acids, followed by a collagen-like region. The sclA gene was found to be positively regulated by Mga, a transcriptional activator of several S. pyogenes virulence determinants. A mutant lacking cell wall-associated SclA was... (More)
Surface proteins of Streptococcus pyogenes are important virulence factors. Here we describe a novel collagen-like surface protein, designated SclA (streptococcal collagen-like surface protein). The sclA gene was identified in silico using the Streptococcal Genome Sequencing Project with the recently identified protein GRAB as the probe. SclA has a signal sequence and a cell wall attachment region containing the prototypic LPXTGX motif. The surface-exposed part of SclA contains a unique NH(2)-terminal domain of 73 amino acids, followed by a collagen-like region. The sclA gene was found to be positively regulated by Mga, a transcriptional activator of several S. pyogenes virulence determinants. A mutant lacking cell wall-associated SclA was constructed and was found to be as effective as wild-type bacteria in platelet aggregation, survival in fresh human blood, and adherence to pharyngeal cells. The sclA gene was found in all 12 S. pyogenes strains that were investigated using PCR. Sequence analysis revealed that the signal sequence and the cell wall attachment region are highly conserved. The collagen-like domain is variable in its NH(2)-terminal region and has conserved repeated domains in its COOH-terminal part. SclA proteins from most strains have additional proline-rich repeats spacing the collagen-like domain and the cell wall attachment sequence. The unique NH(2)-terminal region is hypervariable, but computer predictions indicate a common secondary structure, with two alpha helices connected by a loop region. Immune selection may explain the hypervariability in the NH(2)-terminal region, whereas the preserved secondary structure implies that this region has a common function. These features and the Mga regulation are shared with the M protein of S. pyogenes. Moreover, as with the gene encoding the M protein, phylogenetic analysis indicates that horizontal gene transfer has contributed to the evolution of sclA. (Less)
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author
organization
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Contribution to journal
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published
subject
in
Infection and Immunity
volume
68
issue
11
pages
6370 - 6377
publisher
American Society for Microbiology
external identifiers
  • pmid:11035747
  • scopus:0033793665
ISSN
1098-5522
language
English
LU publication?
yes
id
3e643d38-12ed-4764-9a80-3a59d2955351 (old id 1118191)
alternative location
http://iai.asm.org/cgi/content/abstract/68/11/6370
date added to LUP
2008-06-18 13:13:45
date last changed
2017-03-26 03:32:16
@article{3e643d38-12ed-4764-9a80-3a59d2955351,
  abstract     = {Surface proteins of Streptococcus pyogenes are important virulence factors. Here we describe a novel collagen-like surface protein, designated SclA (streptococcal collagen-like surface protein). The sclA gene was identified in silico using the Streptococcal Genome Sequencing Project with the recently identified protein GRAB as the probe. SclA has a signal sequence and a cell wall attachment region containing the prototypic LPXTGX motif. The surface-exposed part of SclA contains a unique NH(2)-terminal domain of 73 amino acids, followed by a collagen-like region. The sclA gene was found to be positively regulated by Mga, a transcriptional activator of several S. pyogenes virulence determinants. A mutant lacking cell wall-associated SclA was constructed and was found to be as effective as wild-type bacteria in platelet aggregation, survival in fresh human blood, and adherence to pharyngeal cells. The sclA gene was found in all 12 S. pyogenes strains that were investigated using PCR. Sequence analysis revealed that the signal sequence and the cell wall attachment region are highly conserved. The collagen-like domain is variable in its NH(2)-terminal region and has conserved repeated domains in its COOH-terminal part. SclA proteins from most strains have additional proline-rich repeats spacing the collagen-like domain and the cell wall attachment sequence. The unique NH(2)-terminal region is hypervariable, but computer predictions indicate a common secondary structure, with two alpha helices connected by a loop region. Immune selection may explain the hypervariability in the NH(2)-terminal region, whereas the preserved secondary structure implies that this region has a common function. These features and the Mga regulation are shared with the M protein of S. pyogenes. Moreover, as with the gene encoding the M protein, phylogenetic analysis indicates that horizontal gene transfer has contributed to the evolution of sclA.},
  author       = {Rasmussen, Magnus and Eden, A and Björck, Lars},
  issn         = {1098-5522},
  language     = {eng},
  number       = {11},
  pages        = {6370--6377},
  publisher    = {American Society for Microbiology},
  series       = {Infection and Immunity},
  title        = {SclA, a novel collagen-like surface protein of Streptococcus pyogenes},
  volume       = {68},
  year         = {2000},
}