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. <i>Staphylococcus aureus</i> UAMS-1 is a clinical isolate that codes for two hyaluronidases (<i>hysA1</i> and <i>hysA2</i>). Previous research has shown the presence of a full-length HysA1 protein from the <i>S. aureus</i> UAMS-1 strain with no evidence of enzymatic activity. A single base change resulting in an E480G amino acid change was identified in the <i>S. aureus</i> UAMS-1 <i>hysA1</i> gene when compared to the <i>S. aureus</i> Sanger 252 <i>hysA1</i> gene. A plasmid copy of the <i>S. aureus</i> Sanger 252 <i>hysA1 </i>gene transduced into a <i>hysA2 </i>deletion mutant strain of <i>S. aureus</i> 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 <i>S. aureus</i> UAMS-1 strain is most likely caused by the mutation identified in our study.

Complete genome sequencing and comparative genomic analysis of three donkey Streptococcus equi subsp. equi isolates

“…Hyaluronic acid (HA) is a linear anionic, non-sulfated, heteropolysaccharide composed of glucuronic acid and N-acetylglucosamine joined alternately by β glycosidic bonds (Marinho et al, 2021). Most bacterial hyaluronidase is believed to facilitate the pathogen's invasion and survival in the host, which is critical to its pathogenicity and gives the pathogens an evolutionary advantage (Hynes et al, 2000;Desiere et al, 2001;Smith et al, 2005;Messina et al, 2016;Hu et al, 2021). It was reported that a few microorganisms of groups A and C streptococci are HA producers (Wei et al, 2012).…”