The characterization of GAS hyaluronidase

性状（由申请方提供）：A组链球菌（GAS）依赖透明质酸（HA）荚膜逃避吞噬作用并与宿主细胞结合。特异性地，GAS还产生透明质酸酶（HYL），一种切割HA的酶。通常认为HYL作用于人体组织基质中结构相同的HA，以促进生物体的扩散，然而这种假设尚未得到正式验证。初步数据表明，HYL的产生在皮肤感染的小鼠模型中对感染的传播没有明显的作用。数据还表明，HYL+菌株能够在单独的HA上存活，这表明HYL的可能功能可能是通过消耗其自身的胶囊来帮助在营养缺乏条件下的存活。对HYL+和HYL-菌株中hylA基因的遗传分析表明，在HYL-菌株中存在一个提前终止密码子，从而避免了该基因的可能消除。具体目的是1）确定化脓链球菌透明质酸酶是否是皮肤和软组织感染小鼠模型中的扩散因子。2)表征GAS透明质酸酶在生长和营养缺乏期间可能的营养作用。3）确定Hyl-菌株的hylA基因是否产生无酶活性但起替代作用的产物。

DESCRIPTION (provided by applicant): Group A streptococci (GAS) depend on a hyaluronic acid (HA) capsule for evasion of phagocytosis and for binding to host cells. Paradoxically GAS also produces hyaluronidases (HYL), enzymes that cleave HA. It is commonly assumed that HYL acts on structurally identical HA in human tissue matrix to promote spread of the organism, however this assumption has not been tested formally. Preliminary data indicates that production of HYL has no apparent effect in spread of infection in murine model of skin infection. Data also indicates that HYL+ strains are able to survive on HA alone, suggesting a possible function of HYL may be to aid in survival in nutrient deprived conditions by consuming its own capsule. Genetic analysis of hylA gene in HYL+ and HYL- strains indicates a premature stop codon in HYL- strains, eluding to a possible elimination of this gene. The specific aims are 1) to determine if Streptococcus pyogenes hyaluronidase is a spreading factor in a murine model of skin and soft tissue infection. 2) to characterize a possible nutritional role for GAS hyaluronidase during growth and nutrient deprivation.3) to determine whether the hylA genes of Hyl- strains produce a product that is not enzymatically active but serves an alternative role.