Unique regulation of SclB - a novel collagen-like surface protein of Streptococcus pyogenes

Slipped-strand mispairing at sites containing so-called coding repeats (CRs ) can lead to phase variation of surface proteins in Gram-negative bacteria . This mechanism, believed to contribute to virulence, has so far not been identified in a Gram-positive bacterium. In the genome of the Gram-positive human pathogen Streptococcus pyogenes, we identified pentanucleotide CRs w ithin a putative signal sequence of an open reading frame (ORF) encoding a novel collagen-like surface protein, denoted SclB. In 12 S. pyogenes strain s, the number of CRs in the sclB gene varied from three to 19, rendering th e start codon in frame with the downstream ORF in four strains and out of f rame in eight strains. A protein reacting with anti-SclB antibodies could o nly be solubilized from three strains, all containing an intact sclB gene. Variations in the number of CRs were observed within strains of the same M serotype and occurred during growth of S. pyogenes in fresh human blood, bu t not in medium. The SclB protein has a hypervariable N-terminal part, a co llagen-like central part and a typical cell wall sorting sequence containin g the LPXTGX motif. SclB is related to the collagen-like SclA and is, like SclA, involved in the adhesion of S. pyogenes bacteria to human cells. Howe ver, the Mga protein, known to upregulate sclA and several additional genes encoding virulence factors of S. pyogenes, downregulates sclB transcriptio n. This observation and the potential of SclB to phase vary by slipped-stra nd mispairing emphasize the unique regulation of this novel S. pyogenes sur face protein.