Characterization of the Group B Streptococcal Hyaluronate Lyase

Extracellular virulence factors of group B Streptococci

“…Pritchard, on careful studies, identified that the compound released in the assay is actually a derivative of hyaluronic acid contaminating the mucin preparation (37). On encountering hyaluronan, GBS hyaluronate lyase makes random cuts in the substrate chain and releases disaccharides as it proceeds along the molecule (38). Details of this enzymatic activity were predicted based on the crystal structures of GBS hyaluronate lyase, and their complexes with both a disaccharide product of degradation, and a hexasaccharide unit of hyaluronan (39,40).…”

The Prophage-encoded Hyaluronate Lyase Has Broad Substrate Specificity and Is Regulated by the N-terminal Domain

“…Phage HLs Show Substrate Inhibition-The HLs (bacterial as well as prophage encoded) act readily on HA, although only the bacterial extracellular HL degrades CS-C, albeit only with ϳ8 -10% as compared with HA (15). The reason for phage HLs to have absolute substrate specificity for HA is not known.…”

“…The role of phage HLs in pathogenesis or generating nutrient source was ruled out (5,9,(12)(13)(14). Conversely, a few studies have reported an antibody response to phage-encoded HLs during S. equi and S. pyogenes infection, increased tissue permeability after exposure to HL, and conversion of S. pyogenes from non-infective to toxigenic after infection with bacteriophage (9,15,16). Most importantly, in the clinical strain S. equi 4047, the only functional HL is of phage origin, and the bacteria-encoded HL is nonfunctional due to the truncation of the catalytic C-terminal region (5,17).…”

Insights into the Mechanism of Action of Hyaluronate Lyase

“…Group B streptococci (GBS) possess a variety of virulence factors. Hyaluronate lyase (HL), 2 a potential virulence determinant, is produced as an extracellular enzyme by most strains of GBS (3). Virulent Streptococcus agalactiae isolates associated with invasive disease are known to produce higher levels of extracellular hyaluronate lyases (4).…”

“…Crystal structures of both the HLs suggest that they are similar in whole structure architecture, and the active site geometry except for the spacer domain that is only present in SagHL (18). Although no calcium binding sites are observed on these enzymes,theirenzymaticactivitiesarereportedtobecalciumdependent (3,14,21). Recently significant emphasis has been put on proposing specific details of the mechanism of HL activity (16 -20).…”