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Role of Hyaluronidase in Subcutaneous Spread and Growth of Group A Streptococcus

机译:透明质酸酶在A组链球菌皮下扩散和生长中的作用

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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.
机译:A组链球菌(GAS)依赖于透明质酸(HA)胶囊来逃避吞噬作用并与上皮细胞相互作用。矛盾的是,GAS还产生透明质酸酶(Hyl),一种切割HA的酶。一个普遍的假设是,Hyl会在人体组织中消化结构相同的HA,从而促进细菌扩散。我们在临床Hyl + 分离物中灭活了编码细胞外透明质酸酶 hylA 的基因。将Hyl + 和同基因的Hyl ?突变体皮下注射到有或没有高分子量葡聚糖蓝的小鼠体内。 Hyl ?菌株产生细小的病灶,染料集中集中。 Hyl + 菌株产生相同的病灶,但染料在皮下扩散。然而,Hyl + 细菌并不是从未受染料扩散染色的皮肤中分离出来的。因此,Hyl消化组织HA并促进大分子的扩散,但是不足以引起细菌的皮下扩散或影响病变的大小。在培养液中定期检测GAS胶囊的表达,并且在活性胶囊合成的开始和结束时,相对于Hyl ?菌株,Hyl + 菌株中的表达降低,但在峰合成期间则不降低在指数中期。因此,Hyl的活性不足以在峰合成过程中去除胶囊。为证明Hyl可能的营养作用,GAS被证明与唯一的碳源一起生长,但仅含N-乙酰氨基葡萄糖而不是d-葡萄糖醛酸(HA的两个组分)。然而,只有Hyl + 菌株可以利用HA作为唯一的碳源生长,这表明Hyl可以允许生物利用宿主HA或自身的胶囊作为能源。

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