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.

Two Novel Functions of Hyaluronidase from Streptococcus agalactiae Are Enhanced Intracellular Survival and Inhibition of Proinflammatory Cytokine Expression

“…The data shown are means Ϯ SEM from three independent experiments. transported and metabolized intracellularly to supply the required nutrients (as a carbon source) for a pathogen as it replicates and spreads (16). By analogy with what is observed in other bacteria (32,42), our study showed that S. agalactiae could grow utilizing HA as its sole source of carbon.…”

“…Many pathogenic bacteria produce hyaluronidases, which serve as virulence factors (16). Since hyaluronan is a major constituent of the ground substance of most connective tissues, hyaluronidase may be an essential factor in enabling the spread of the pathogens from an initial site of infection (38).…”

“…Since HA is a major constituent of the ground substance of most connective tissues, particularly the skin, Hyl may be an essential component in enabling the spread of the pathogens from an initial site of infection. Hyaluronidase production has been reported in some Streptococcus species (16). To date, numerous suggestions have been made as to the role of hyaluronidase in the infection process with Streptococcus spp.…”

Hyaluronan Modulation Impacts Staphylococcus aureus Biofilm Infection

“…It should be noted, however, that the preponderance of evidence demonstrating the immunogenic effects of low-molecular-mass HA fragments have studied HA fragments generated by mammalian hyaluronidases or catabolically equivalent microbial enzymes (i.e., Streptomyces HysA) that yield polymeric products (tetrasaccharides and oligosaccharides) of a similar size range (4-to 16-mers) (17,(58)(59)(60)(61). In contrast, HysA from S. aureus and other Gram-positive pathogens (e.g., group A streptococci and S. agalactiae) possess greater enzymatic processivity and break down HA into disaccharide units (62). Inactivation of hyaluronidase in S. agalactiae elicits enhanced cytokine responses from both macrophage cultures and splenic homogenates following infectious challenge (54), suggesting that such catabolic end products may actually promote immune evasion.…”

Group A streptococcus cell‐associated pathogenic proteins as revealed by growth in hyaluronic acid‐enriched media

“…To invade the connective tissue of the human host, GAS produces hyaluronate lyases that depolymerise HA [5]. The result of the enzymatic depolymerisation of HA is a decrease in the viscosity of the extracellular matrix, and therefore increased permeability of the connective tissues, and potentially an increase in pathogen aggression, and diffusion of its toxins, through the connective tissue [6]. In addition to hyaluronate lyases, many other factors are known to contribute to streptococcal virulence, such as M proteins, lipoteichoic acid, the HA capsule that surrounds the pathogen, pyrogenic exotoxins, streptolysins and C5a peptidase [7].…”