The lone S41 family C-terminal processing protease in Staphylococcus aureus is localized to the cell wall and contributes to virulence
The lone S41 family C-terminal processing protease in Staphylococcus aureus is localized to the cell wall and contributes to virulence
复制标题
DOI：
10.1099/mic.0.079798-0
复制
发表时间：
2014-08-01
期刊：
影响因子：
2.8
通讯作者：
Shaw, Lindsey N.
中科院分区：
文献类型：
--
作者：
Carroll, Ronan K.;Rivera, Frances E.;Shaw, Lindsey N.
金黄色葡萄球菌是人类的一种多功能病原体，由于多重耐药菌株的增加和传播，一直是一个公共卫生问题。作为对金黄色葡萄球菌致病机制正在进行的研究的一部分，我们先前证明了金黄色葡萄球菌的毒力需要一个细胞内的N末端加工酶。在此基础上，我们研究了金黄色葡萄球菌唯一的C末端加工酶CTPA的作用。CTPA是S41家族的成员之一，是一种丝氨酸蛋白酶，其在革兰氏阴性菌中的同源物参与了包括致病在内的一系列生物学功能。我们证明，金黄色葡萄球菌CTPA定位于细菌细胞壁，CTPA基因的表达在感染过程中遇到的条件下达到最大。当CTPA基因被破坏时，当接触到宿主免疫系统的组件时，会导致耐热性降低和敏感性增加。最后，我们证明了CTPA(-)突变株在小鼠感染模型中的毒力减弱。我们的结果首次表征了致病性革兰氏阳性细菌中的C末端加工酶，并表明它在感染过程中发挥着关键作用。
Staphylococcus aureus is a versatile pathogen of humans and a continued public health concern due to the rise and spread of multidrug-resistant strains. As part of an ongoing investigation into the pathogenic mechanisms of this organism we previously demonstrated that an intracellular N-terminal processing protease is required for S. aureus virulence. Following on from this, here we examine the role of CtpA, the lone C-terminal processing protease of S. aureus. CtpA, a member of the S41 family, is a serine protease whose homologues in Gram-negative bacteria have been implicated in a range of biological functions, including pathogenesis. We demonstrate that S. aureus CtpA is localized to the bacterial cell wall and expression of the ctpA gene is maximal upon exposure to conditions encountered during infection. Disruption of the ctpA gene leads to decreased heat tolerance and increased sensitivity when exposed to components of the host immune system. Finally we demonstrate that the ctpA(-) mutant strain is attenuated for virulence in a murine model of infection. Our results represent the first characterization of a C-terminal processing protease in a pathogenic Gram-positive bacterium and show that it plays a critical role during infection.