Department of Cell Biology, Microbiology & Molecular Biology, University of South Florida, Tampa, FL, USA.
Microbiology (Reading). 2014 Aug;160(Pt 8):1737-1748. doi: 10.1099/mic.0.079798-0. Epub 2014 Jun 13.
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.
金黄色葡萄球菌是人类的一种多功能病原体，由于多药耐药菌株的出现和传播，它一直是公共卫生关注的问题。作为我们对该生物体致病机制的持续研究的一部分，我们之前证明了一种细胞内 N 端加工蛋白酶是金黄色葡萄球菌毒力所必需的。在此基础上，我们在这里研究了金黄色葡萄球菌中唯一的 C 端加工蛋白酶 CtpA 的作用。CtpA 是 S41 家族的成员，是一种丝氨酸蛋白酶，革兰氏阴性菌中的同源物与多种生物学功能有关，包括发病机制。我们证明金黄色葡萄球菌 CtpA 定位于细菌细胞壁，并且当暴露于感染过程中遇到的条件时，ctpA 基因的表达达到最大值。ctpA 基因的破坏导致耐热性降低，并且当暴露于宿主免疫系统的成分时敏感性增加。最后，我们证明 ctpA(-)突变株在感染的小鼠模型中毒力减弱。我们的结果代表了对致病性革兰氏阳性菌中的 C 端加工蛋白酶的首次表征，并表明它在感染过程中起着关键作用。
