title: Streptococcal histone-like protein: primary structure of hlpA and protein binding to lipoteichoic acid and epithelial cells.
abstract: In addition to its role in the nucleoid, the histone-like protein (HlpA) of Streptococcus pyogenes is believed to act as a fortuitous virulence factor in delayed sequelae by binding to heparan sulfate-proteoglycans in the extracellular matrix of target organs and acting as a nidus for in situ immune complex formation. To further characterize this protein, the hlpA genes were cloned from S. pyogenes, S. gordonii, S. mutans, and S. sobrinus, using PCR amplification, and sequenced. The encoded HlpA protein of S. pyogenes has 91 amino acids, a predicted molecular mass of 9,647 Da, an isoelectric point of 9.81, and 90% to 95% sequence identity with HlpA of several oral streptococci. The consensus sequence of streptococcal HlpA has 69% identity with the consensus sequence of the histone-like HB protein of Bacillus species. Oral viridans group streptococci, growing in chemically defined medium at pH 6.8, released HlpA into the milieu during stationary phase as a result of limited cell lysis. HlpA was not released by these bacteria when grown at pH 6.0 or below. S. pyogenes did not release HlpA during growth in vitro; however, analyses of sera from 155 pharyngitis patients revealed a strong correlation (P < 0.0017) between the production of antibodies to HlpA and antibodies to streptolysin O, indicating that the histone-like protein is released by group A streptococci growing in vivo. Extracellular HlpA formed soluble complexes with lipoteichoic acid in vitro and bound readily to heparan sulfate on HEp-2 cell surfaces. These results support a potential role for HlpA in the pathogenesis of streptococcus-induced tissue inflammation.
authors.affiliation: Department of Microbiology, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, 14214, USA. mstinson@ubmedb.buffalo.edu
authors.forename: M W
authors.initials: MW
authors.lastname: Stinson
authors.forename: R
authors.initials: R
authors.lastname: McLaughlin
authors.forename: S H
authors.initials: SH
authors.lastname: Choi
authors.forename: Z E
authors.initials: ZE
authors.lastname: Juarez
authors.forename: J
authors.initials: J
authors.lastname: Barnard
mesh_terms: D000595:Amino Acid Sequence; D000907:Antibodies, Bacterial / Q000032:analysis; D001407:Bacillus / Q000235:genetics; D001426:Bacterial Proteins; D001483:Base Sequence; D002478:Cells, Cultured; D003001:Cloning, Molecular; D003470:Culture Media / Q000032:analysis / Q000737:chemistry; D004269:DNA, Bacterial / Q000032:analysis / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D015870:Gene Expression; D006497:Heparan Sulfate / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism; D008969:Molecular Sequence Data; D010940:Plant Proteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011485:Protein Binding; D016196:S Phase; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D013291:Streptococcus / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D013301:Streptolysins / Q000276:immunology; D013682:Teichoic Acids / Q000378:metabolism
chemical_list: D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D003470:Culture Media; D004269:DNA, Bacterial; D004268:DNA-Binding Proteins; D006497:Heparan Sulfate; D008070:Lipopolysaccharides; D010940:Plant Proteins; D013301:Streptolysins; D013682:Teichoic Acids; C106634:HLPA protein, Guillardia theta; C025964:streptolysin O; C009900:lipoteichoic acid