A naturally occurring point mutation in the hyaluronidase gene (hysA1) of Staphylococcus aureus UAMS-1 results in reduced enzymatic activity

Abstract

Hyaluronic acid is a high molecular weight polysaccharide that is widely distributed in animal tissues. Bacterial hyaluronidases degrade hyaluronic acid as secreted enzymes and have been shown to contribute to infection. Staphylococcus aureus UAMS-1 is a clinical isolate that codes for two hyaluronidases (hysA1 and hysA2). Previous research has shown the presence of a full-length HysA1 protein from the S. aureus UAMS-1 strain with no evidence of enzymatic activity. A single base change resulting in an E480G amino acid change was identified in the S. aureus UAMS-1 hysA1 gene when compared to the S. aureus Sanger 252 hysA1 gene. A plasmid copy of the S. aureus Sanger 252 hysA1 gene transduced into a hysA2 deletion mutant strain of S. aureus UAMS-1 restored near wild type levels of enzymatic activity. Homology modeling and structural analysis suggested that Glu-480 in the HysA1 is critically responsible for maintaining the structural and functional ensemble of the catalytic and tunnel-forming residues, which are essential for enzyme activity. A high degree of relatedness among several Gram-positive bacterial hyaluronidases indicate the loss of enzymatic activity of HysA1 in the S. aureus UAMS-1 strain is most likely caused by the mutation identified in our study.