title: Unique regulation of SclB - a novel collagen-like surface protein of Streptococcus pyogenes.
abstract: 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 within a putative signal sequence of an open reading frame (ORF) encoding a novel collagen-like surface protein, denoted SclB. In 12 S. pyogenes strains, the number of CRs in the sclB gene varied from three to 19, rendering the start codon in frame with the downstream ORF in four strains and out of frame in eight strains. A protein reacting with anti-SclB antibodies could only 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, but not in medium. The SclB protein has a hypervariable N-terminal part, a collagen-like central part and a typical cell wall sorting sequence containing 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. However, the Mga protein, known to upregulate sclA and several additional genes encoding virulence factors of S. pyogenes, downregulates sclB transcription. This observation and the potential of SclB to phase vary by slipped-strand mispairing emphasize the unique regulation of this novel S. pyogenes surface protein.
authors.affiliation: Section for Molecular Pathogenesis, Department of Cell and Molecular Biology, Lund University, BMC, B14, Tornavägen 10, S-221 84 Lund, Sweden. Magnus.Rasmussen@medkem.lu.se
authors.forename: M
authors.initials: M
authors.lastname: Rasmussen
authors.forename: L
authors.initials: L
authors.lastname: Björck
mesh_terms: D000595:Amino Acid Sequence; D001422:Bacterial Adhesion / Q000502:physiology; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D002478:Cells, Cultured; D003001:Cloning, Molecular; D003094:Collagen / Q000737:chemistry; D005347:Fibroblasts / Q000382:microbiology; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D010609:Pharyngeal Muscles / Q000166:cytology / Q000382:microbiology; D012091:Repetitive Sequences, Nucleic Acid; D012703:Serotyping; D013297:Streptococcus pyogenes / Q000145:classification / Q000502:physiology*; D015854:Up-Regulation
chemical_list: D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; C433523:SclB protein, Streptococcus pyogenes; C068267:mry protein, Streptococcus pyogenes; D003094:Collagen