Type VI secretion system contributes to Enterohemorrhagic Escherichia coli virulence by secreting catalase against host reactive oxygen species (ROS).
Type VI secretion system contributes to Enterohemorrhagic Escherichia coli virulence by secreting catalase against host reactive oxygen species (ROS).
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VI 型分泌系统通过分泌过氧化氢酶对抗宿主活性氧 (ROS)，从而增强肠出血性大肠杆菌的毒力
DOI：
10.1371/journal.ppat.1006246
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发表时间：
2017-03
期刊：
影响因子：
6.7
通讯作者：
Yao YF
中科院分区：
文献类型：
--
作者：
Wan B;Zhang Q;Ni J;Li S;Wen D;Li J;Xiao H;He P;Ou HY;Tao J;Teng Q;Lu J;Wu W;Yao YF
肠出血性大肠杆菌（EHEC）是一种主要的食源性致病菌。VI型分泌系统（T6 SS）参与了细菌的致病性和细菌间的竞争。在这里，我们表明，肠出血性大肠杆菌可以分泌一种新的效应KatN，锰含过氧化氢酶，在T6 SS依赖的方式。katN的表达由RpoS和OxyR促进，由H-NS抑制，并且katN有助于体外氧化应激下的细菌生长。EHEC被巨噬细胞吞噬后，KatN可分泌到宿主细胞胞浆中，导致细胞内活性氧水平降低，有利于EHEC在巨噬细胞内的存活。最后，动物模型结果表明，T6 SS的缺失突变体的毒力与野生型菌株相比减弱，而katN的缺失突变体的毒力与野生型菌株相当。以上结果提示，EHEC可能通过分泌过氧化氢酶KatN来感受吞噬体的氧化应激，降低宿主细胞内的ROS水平，从而促进其在宿主细胞内的存活。VI型分泌系统（T6 SS）是一种特异性的大分子蛋白质输出系统，广泛分布于革兰氏阴性菌中。T6 SS在真核宿主的抗细菌竞争和毒力中起重要作用。肠出血性大肠杆菌（EHEC）可引起严重的食源性疾病，包括腹部绞痛和腹泻，可能发展为出血性腹泻和溶血性尿毒综合征。在目前的研究中，我们表明，EHEC的T6 SS参与其在小鼠细胞内的存活和毒力。具体而言，新的效应KatN，锰-过氧化氢酶在这项工作中确定更新的一般作用的T6 SS在肠出血性大肠杆菌的发病机制，在宿主细胞质中的氧化应激的背景下。结合KatN在含T6 SS细菌中的偏向性分布，我们的数据表明，KatN作为一种新的T6 SS效应子，是T6 SS+细菌致病的关键毒力因子。
Enterohemorrhagic Escherichia coli (EHEC) is one major type of contagious and foodborne pathogens. The type VI secretion system (T6SS) has been shown to be involved in the bacterial pathogenicity and bacteria-bacteria competition. Here, we show that EHEC could secrete a novel effector KatN, a Mn-containing catalase, in a T6SS-dependent manner. Expression of katN is promoted by RpoS and OxyR and repressed by H-NS, and katN contributes to bacterial growth under oxidative stress in vitro. KatN could be secreted into host cell cytosol after EHEC is phagocytized by macrophage, which leads to decreased level of intracellular reactive oxygen species (ROS) and facilitates the intramacrophage survival of EHEC. Finally, animal model results show that the deletion mutant of T6SS was attenuated in virulence compared with the wild type strain, while the deletion mutant of katN had comparable virulence to the wild type strain. Taken together, our findings suggest that EHEC could sense oxidative stress in phagosome and decrease the host cell ROS by secreting catalase KatN to facilitate its survival in the host cells. The type VI secretion system (T6SS) is a specific macromolecular protein export apparatus, and widely distributed in Gram-negative bacteria. Generally, T6SS has been shown to play an important role in anti-bacterial competition and virulence to eukaryotic hosts. Enterohemorrhagic Escherichia coli (EHEC) can cause severe foodborne disease, including abdominal cramps and diarrhea that may progress to bloody diarrhea and hemolytic uremic syndrome. In the current study, we show that the T6SS of EHEC is involved in its intracellular survival and virulence in mice. Specifically, the novel effector KatN, a Mn-catalase identified in this work updates the general role of the T6SS in the pathogenesis of EHEC, in the context of oxidative stress in host cytoplasm. Combined with the biased distribution of katN in the T6SS-containing bacteria, our data suggest that KatN, as a new T6SS effector, is a key virulence factor in the pathogenesis of T6SS+ bacteria.