title: Role of hyaluronidase in subcutaneous spread and growth of group A streptococcus.
abstract: Group A streptococcus (GAS) depends on a hyaluronic acid (HA) capsule to evade phagocytosis and to interact with epithelial cells. Paradoxically, GAS also produces hyaluronidase (Hyl), an enzyme that cleaves HA. A common assumption is that Hyl digests structurally identical HA in human tissue to promote bacterial spread. We inactivated the gene encoding extracellular hyaluronidase, hylA, in a clinical Hyl(+) isolate. Hyl(+) and an isogenic Hyl(-) mutant were injected subcutaneously into mice with or without high-molecular-weight dextran blue. The Hyl(-) strain produced small lesions with dye concentrated in close proximity. The Hyl(+) strain produced identical lesions, but the dye diffused subcutaneously. However, Hyl(+) bacteria were not isolated from unaffected skin stained by dye diffusion. Thus, Hyl digests tissue HA and facilitates spread of large molecules but is not sufficient to cause subcutaneous diffusion of bacteria or to affect lesion size. GAS capsule expression was assayed periodically during broth culture and was reduced in Hyl(+) strains relative to Hyl(-) strains at the onset and the end of active capsule synthesis but not during peak synthesis in mid-exponential phase. Thus, Hyl is not sufficiently active to remove capsule during peak synthesis. To demonstrate a possible nutritional role for Hyl, GAS was shown to grow with N-acetylglucosamine but not d-glucuronic acid (both components of HA) as a sole carbon source. However, only Hyl(+) strains could grow utilizing HA as a sole carbon source, suggesting that Hyl may permit the organism to utilize host HA or its own capsule as an energy source.
authors.affiliation: University of Michigan Medical School, Department of Internal Medicine, 3116 TC, Ann Arbor, MI 48109-0378, USA.
authors.forename: Clarise Rivera
authors.initials: CR
authors.lastname: Starr
authors.forename: N Cary
authors.initials: NC
authors.lastname: Engleberg
mesh_terms: D000818:Animals; D016667:Bacterial Capsules / Q000378:metabolism; D003911:Dextrans; D004058:Diffusion; D004195:Disease Models, Animal; D006801:Humans; D006821:Hyaluronoglucosaminidase / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008812:Mice, Hairless; D017422:Sequence Analysis, DNA; D017192:Skin Diseases, Bacterial / Q000201:enzymology* / Q000378:metabolism / Q000382:microbiology; D013290:Streptococcal Infections / Q000201:enzymology* / Q000378:metabolism / Q000382:microbiology; D013297:Streptococcus pyogenes / Q000201:enzymology* / Q000254:growth & development / Q000472:pathogenicity; D014774:Virulence
chemical_list: D003911:Dextrans; C017080:blue dextran; D006821:Hyaluronoglucosaminidase