Hyaluronidases of Gram-positive bacteria

Abstract

Bacterial hyaluronidases, enzymes capable of breaking down hyaluronate, are produced by a number of pathogenic Gram-positive bacteria that initiate infections at the skin or mucosal surfaces. Since reports of the hyaluronidases first appeared, there have been numerous suggestions as to the role of the enzyme in the disease process. Unlike some of the other more well studied virulence factors, much of the information on the role of hyaluronidase is speculative, with little or no data to substantiate proposed roles. Over the last 5 years, a number of these enzymes from Gram-positive organisms have been cloned, and the nucleotide sequence determined. Phylogenetic analysis, using the deduced amino acid sequences of the Gram-positive hyaluronidases, suggests a relatedness among some of the enzymes. Molecular advances may lead to a more thorough understanding of the role of hyaluronidases in bacterial physiology and pathogenesis. ß

Hyaluronan Binding and Degradation byStreptococcus agalactiae Hyaluronate Lyase

“…Various Gram-positive microorganisms including species of Streptococcus, Clostridium, Propionibacterium, Peptostreptococcus, and Streptomyces produce hyaluronate lyase (11). All known bacterial hyaluronate lyases were found to share substantial sequence identity and thus likely to use the similar mechanism for the catalytic action (12).…”

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).…”

“…), 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.…”

Insights into the Mechanism of Action of Hyaluronate Lyase

“…It is part of a large family of enzymes called hyaluronidases, found in many Gram-positive pathogens (6). These enzymes have been postulated to facilitate the spread of bacteria by breaking down HA, a polymer composed of repeating units of D-glucosoamine and D-glucuronic acid (7).…”