STREPTOCOCCAL HISTONE-LIKE PROTEIN - PRIMARY STRUCTURE OF HLPA AND PROTEIN-BINDING TO LIPOTEICHOIC ACID AND EPITHELIAL-CELLS

In addition to its role in the nucleoid, the histone-like protein (Hlp A) of Streptococcus pyogenes is believed to act as a fortuitous virule nce factor in delayed sequelae by binding to heparan sulfate-proteogly cans in the extracellular matrix of target organs and acting as a nidu s for in situ immune complex formation. To further characterize this p rotein, the hlpA genes were cloned from S. pyogenes, S. gordonii, S. m utans, and S. sobrinus, using PCR amplification, and sequenced. The en coded HlpA protein of S. pyogenes has 91 amino acids, a predicted mole cular mass of 9,647 Da, an isoelectric point of 9.81, and 90% to 95% s equence identity with HlpA of several oral streptococci. The consensus sequence of streptococcal HlpA has 69% identity with the consensus se quence of the histone-like HE protein of Bacillus species. Oral virida ns 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 reveal ed a strong correlation (P < 0.0017) between the production of antibod ies to HlpA and antibodies to streptolysin O, indicating that the hist one-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. The se results support a potential role for HlpA in the pathogenesis of st reptococcus-induced tissue inflammation.