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

Surface proteins of Streptococcus pyogenes are important virulence factors. Here we describe a novel collagenlike surface protein, designated SclA (st reptococcal 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 cel l wall attachment region containing the prototypic LPXTGX motif. The surfac e-exposed part of SclA contains a unique NH2-terminal domain of 73 amino ac ids, followed by a collagen-like region. The sclA gene was found to be posi tively regulated by Mga, a transcriptional activator of several S. pyogenes virulence determinants. A mutant lacking cell wall-associated SclA was con structed and was found to be as effective as wild-type bacteria in platelet aggregation, survival in fresh human blood, and adherence to pharyngeal ce lls. The sclA gene was found in all 12 S. pyogenes strains that were invest igated using PCR Sequence analysis revealed that the signal sequence and th e cell wall attachment region are highly conserved. The collagen-like domai n 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 at tachment sequence. The unique NH2-terminal region is hypervariable, but com puter predictions indicate a common secondary structure, with two alpha hel ices connected by a loop region. Immune selection may explain the hypervari ability in the NH2-terminal region, whereas the preserved secondary structu re implies that this region has a common function. These features and the M ga regulation are shared with the M protein of S. pyogenes. Moreover, as wi th the gene encoding the M protein, phylogenetic analysis indicates that ho rizontal gene transfer has contributed to the evolution of sclA.