The Streptococcus equi prophage-encoded protein SEQ2045 is a hyaluronan-specific hyaluronate lyase that is produced during equine infection

Abstract

Streptococcus equi causes equine ‘strangles’. Hyaluronate lyases, which degrade connective tissue hyaluronan and chondroitins, are thought to facilitate streptococcal invasion of the host. However, prophage-encoded hyaluronate lyases are hyaluronan-specific and are thought to be primarily involved in the degradation of the hyaluronan capsule of streptococci during bacteriophage infection. To understand the role of prophage-encoded hyaluronate lyases further, we have biochemically characterized such a hyaluronate lyase, SEQ2045 from S. equi, and have shown that it is produced during equine infection. Prophage-encoded hyaluronan-specific hyaluronate lyases may therefore play a more direct role in disease pathogenesis than previously thought.

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

“…HylP2) lack the signal peptide, and hence, HL activity has not been observed in the extracellular milieu of either S. equi or S. pyogenes infected with temperate bacteriophage (5,9,12,13). The phage HLs have been reported to be specific to HA and do not cleave CS-C and DS (5,12,13).…”

“…The phage HLs have been reported to be specific to HA and do not cleave CS-C and DS (5,12,13). Furthermore, unlike the extracellular bacterial HLs of pathogenic streptococci (Streptococcus agalactiae, Streptococcus pneumoniae, S. pyogenes etc.…”

“…Furthermore, unlike the extracellular bacterial HLs of pathogenic streptococci (Streptococcus agalactiae, Streptococcus pneumoniae, S. pyogenes etc. ), which completely degrade HA to disaccharides (⌬HA 2 ) by processive mode of cleavage, the phage HLs are reported to produce tetra-decasaccharides (⌬HA 4 -⌬HA 10 ) only by random cleavage (5,(12)(13)(14). The disaccharides are useful nutrients that support bacterial proliferation in the host tissue (9).…”

“…The potential role of phage HLs has thus been postulated to cleave streptococci HA capsule to reduce the viscosity of HA in the immediate vicinity of phage particles for bacterial lysogenization. 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).…”

“…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). In light of the above observations, it appeared necessary to re-evaluate the role of phage HL as a virulence factor.…”