SclA, a Novel Collagen-Like Surface Protein ofStreptococcus pyogenes

• DOI: 10.1128/iai.68.11.6370-6377.2000
• Publication Date: 2002-07-27T10:01:09Z
• Authors: Magnus Rasmussen; Arvid Edén; Lars Björck
• Keywords: 0301 basic medicine; Antigens, Bacterial; 0303 health sciences; Base Sequence; Transcription, Genetic; Streptococcus pyogenes; Molecular Sequence Data; 03 medical and health sciences; Bacterial Proteins; Animals; Collagen; Rabbits; Carrier Proteins; Bacterial Outer Membrane Proteins

ABSTRACTSurface proteins ofStreptococcus pyogenesare important virulence factors. Here we describe a novel collagen-like surface protein, designated SclA (streptococcal collagen-like surface protein). ThesclAgene 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 NH2-terminal domain of 73 amino acids, followed by a collagen-like region. ThesclAgene was found to be positively regulated by Mga, a transcriptional activator of severalS. pyogenesvirulence 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. ThesclAgene was found in all 12S. pyogenesstrains 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 NH2-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 NH2-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 NH2-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 ofS. pyogenes. Moreover, as with the gene encoding the M protein, phylogenetic analysis indicates that horizontal gene transfer has contributed to the evolution ofsclA.