The characterization of GAS hyaluronidase

描述（由申请人提供）：A组链球菌（GAS）依赖透明质酸（HA）胶囊来逃避吞噬作用并与宿主细胞结合。矛盾的是，GAS 还会产生透明质酸酶 (HYL)，即裂解 HA 的酶。人们普遍认为 HYL 作用于人体组织基质中结构相同的 HA，以促进生物体的传播，但这一假设尚未经过正式测试。初步数据表明，HYL 的产生对小鼠皮肤感染模型中的感染传播没有明显影响。数据还表明，HYL 菌株能够仅依靠 HA 生存，这表明 HYL 的一个可能功能可能是通过消耗其自身的胶囊来帮助在营养匮乏的条件下生存。 HYL 和 HYL- 菌株中 hylA 基因的遗传分析表明 HYL- 菌株中存在过早终止密码子，从而避免了该基因可能被消除的情况。具体目标是 1) 确定化脓性链球菌透明质酸酶是否是小鼠皮肤和软组织感染模型中的传播因子。 2) 表征GAS透明质酸酶在生长和营养缺乏过程中可能的营养作用。3) 确定Hyl-菌株的hylA基因是否产生不具有酶活性但具有替代作用的产物。

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.