A single nucleotide mutation results in loss of enzymatic activity in the hyaluronate lyase gene of Streptococcus pyogenes.

Group A streptococci produce a variety of extracellular proteins, many of which are considered to be virulence factors. One of these is hyaluronate lyase (HylA), an enzyme capable of degrading the extracellular matrix of the host as well as the bacterial capsule. The current study examined three genotypes of hylA (full, truncated and deleted). Only isolates containing a full-length gene produced an enzymatically active hyaluronate lyase; however, truncation of the protein was not the reason for loss of activity. A single nucleotide substitution, resulting in an amino acid change at position 199 of the lyase was present in a highly-conserved region of the protein in isolates not producing active enzyme. In serotypes 4 and 22, those producing active enzymes, this residue was an aspartic acid, in serotypes not showing hyaluronate lyase activity, it was a valine. Site-directed mutagenesis indicated the loss of enzymatic activity of the hyaluronate lyase is in part determined by the mutation resulting in an amino acid residue change. This mutation results in an inactive form of the enzyme and is found in the more virulent serotypes of Streptococcus pyogenes, suggesting that hyaluronate lyase could interfere with the disease process, in essence being an anti-virulence factor.