The type VII secretion system of Staphylococcus aureus secretes a nuclease toxin that targets competitor bacteria.
The type VII secretion system of Staphylococcus aureus secretes a nuclease toxin that targets competitor bacteria.
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DOI：
10.1038/nmicrobiol.2016.183
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发表时间：
2016-10-10
影响因子：
28.3
通讯作者：
Palmer T
中科院分区：
文献类型：
--
作者：
Cao Z;Casabona MG;Kneuper H;Chalmers JD;Palmer T
VII型蛋白分泌系统(T7SS)在包括结核分枝杆菌和金黄色葡萄球菌在内的人类病原体的毒力中起着关键作用。在此，我们报道了金黄色葡萄球菌T7SS分泌一种大的核酸酶毒素ESAD。ESAD的毒性活性在其生物合成过程中通过与抗毒素ESAG形成络合物而被中和，ESAG与其C-末端核酸酶结构域结合。ESAD的分泌依赖于另一种辅助蛋白EsaE，它不与核酸酶结构域相互作用，而是与ESAD N-末端区域结合。ESAE具有细胞质/膜的双重定位，膜结合的ESAE与T7SS分泌ATPase、ESSC相互作用，提示ESAE将EsaDG复合体靶向分泌器官。ESAD和ESAE是共分泌的，而ESAG只存在于细胞质中，在分泌过程中可能被剥离。缺乏ESAD的金黄色葡萄球菌的菌株变种编码至少两个EsaG样蛋白，最有可能保护自己免受ESAD+菌株分泌的ESAD的毒力。为了支持这一点，过量生产ESAD的菌株对敏感菌株产生了显著的生长抑制。我们得出结论，T7SS可能在细菌竞争中发挥意想不到的关键作用。
The type VII protein secretion system (T7SS) plays a critical role in the virulence of human pathogens including Mycobacterium tuberculosis and Staphylococcus aureus. Here we report that the S. aureus T7SS secretes a large nuclease toxin, EsaD. The toxic activity of EsaD is neutralised during its biosynthesis through complex formation with an antitoxin, EsaG, which binds to its C-terminal nuclease domain. The secretion of EsaD is dependent upon a further accessory protein, EsaE, that does not interact with the nuclease domain, but instead binds to the EsaD N-terminal region. EsaE has a dual cytoplasmic/membrane localization and membrane-bound EsaE interacts with the T7SS secretion ATPase, EssC, implicating EsaE in targeting the EsaDG complex to the secretion apparatus. EsaD and EsaE are co-secreted whereas EsaG is found only in the cytoplasm and may be stripped off during the secretion process. Strain variants of S. aureus that lack esaD encode at least two copies of EsaG-like proteins most likely to protect themselves from the toxic activity of EsaD secreted by esaD+ strains. In support of this, a strain overproducing EsaD elicits significant growth inhibition against a sensitive strain. We conclude that T7SSs may play unexpected and key roles in bacterial competitiveness.