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化脓性链球菌M3菌毛中T3菌毛蛋白和Cpa菌毛蛋白的连接

Linkage of T3 and Cpa pilins in the Streptococcus pyogenes M3 pilus.

作者信息

Quigley Bernard R, Zähner Dorothea, Hatkoff Matthew, Thanassi David G, Scott June R

机构信息

Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA.

出版信息

Mol Microbiol. 2009 Jun;72(6):1379-94. doi: 10.1111/j.1365-2958.2009.06727.x. Epub 2009 May 8.

Abstract

The important human pathogen Streptococcus pyogenes (group A streptococcus, GAS) initiates infection by pilus-mediated attachment to host tissue. Thus, the pilus is an excellent target for design of anti-infective strategies. The T3 pilus of GAS is composed of multiple covalently linked subunits of the T3 protein to which the two minor pilins, Cpa and OrfB, are covalently attached. Because the proteins of GAS pili do not contain either of the motifs required for pilus polymerization in other Gram-positive bacteria, we investigated the residues involved in their linkage. We show that linkage of Cpa to T3 by the sortase family transpeptidase SrtC2 requires the VPPTG motif in the cell wall-sorting signal of Cpa. We also demonstrate that K173 of T3 is required both for T3 polymerization and for attachment of Cpa to T3. Therefore, attachment of Cpa to K173 of a T3 subunit would block further addition of T3 subunits to this end of the growing pilus. This implies that Cpa is located exclusively at the pilus tip, a location supported by immunogold electron microscopy, and suggests that, as for well-studied pili on Gram-negative bacteria, the role of the pilus is to present the adhesin external to the bacterial capsule.

摘要

重要的人类病原体化脓性链球菌(A组链球菌,GAS)通过菌毛介导附着于宿主组织来引发感染。因此,菌毛是抗感染策略设计的理想靶点。GAS的T3菌毛由多个共价连接的T3蛋白亚基组成,两个次要菌毛蛋白Cpa和OrfB共价连接于其上。由于GAS菌毛蛋白不包含其他革兰氏阳性菌菌毛聚合所需的任何基序,我们研究了参与其连接的残基。我们发现,分选酶家族转肽酶SrtC2将Cpa连接到T3需要Cpa细胞壁分选信号中的VPPTG基序。我们还证明,T3的K173对于T3聚合以及Cpa与T3的连接都是必需的。因此,Cpa与T3亚基的K173连接会阻止T3亚基进一步添加到正在生长的菌毛的这一端。这意味着Cpa仅位于菌毛尖端,免疫金电子显微镜支持这一位置,并表明,与革兰氏阴性菌中研究充分的菌毛一样,菌毛的作用是将粘附素呈现在细菌荚膜外部。

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