Wessels M R, Bronze M S
Channing Laboratory, Brigham and Women's Hospital, Boston, MA.
Proc Natl Acad Sci U S A. 1994 Dec 6;91(25):12238-42. doi: 10.1073/pnas.91.25.12238.
To study the role of the group A streptococcal capsule in pharyngeal colonization, we used two acapsular mutants derived from a type 24 strain of group A Streptococcus by transposon mutagenesis. One mutant had a stable acapsular phenotype due to a transposon-associated chromosomal deletion of essential capsule synthetic genes, while the second mutant could revert to the encapsulated phenotype at a low frequency (< 10(-4)) upon spontaneous excision of the transposon from the capsule-synthesis region of the chromosome. Both acapsular mutants were sensitive to phagocytic killing in vitro and had reduced virulence in mice after intraperitoneal challenge. Mice inoculated intranasally with the stable acapsular mutant rapidly cleared the organisms from the pharynx, and no mice died. In contrast, throat cultures of animals challenged with the revertible mutant yielded many encapsulated revertants, and mortality was similar to that of animals challenged with the parent strain. The rapid emergence of a population of encapsulated revertants in the pharynx implies that the capsule conferred a powerful selective advantage in this environmental niche. Together with the complete avirulence of the stable acapsular mutant, these observations indicate that the hyaluronic acid capsule plays a critical role in colonization and infection of the pharynx by group A streptococci.
为研究A群链球菌荚膜在咽部定植中的作用，我们使用了通过转座子诱变从A群链球菌24型菌株衍生而来的两个无荚膜突变体。一个突变体由于与转座子相关的必需荚膜合成基因的染色体缺失而具有稳定的无荚膜表型，而第二个突变体在转座子从染色体的荚膜合成区域自发切除后，可低频率（<10^(-4)）回复为有荚膜表型。两个无荚膜突变体在体外对吞噬杀伤敏感，腹腔注射攻击后在小鼠中的毒力降低。经鼻接种稳定无荚膜突变体的小鼠迅速从咽部清除了细菌，且无小鼠死亡。相比之下，用可回复突变体攻击的动物的咽喉培养物产生了许多有荚膜的回复株，死亡率与用亲本菌株攻击的动物相似。咽部有荚膜回复株群体的快速出现意味着荚膜在这个生态位中赋予了强大的选择优势。连同稳定无荚膜突变体的完全无毒力，这些观察结果表明透明质酸荚膜在A群链球菌咽部定植和感染中起关键作用。
