TEDA Institute of Biological Sciences and Biotechnology, Nankai Universitygrid.216938.7, Tianjin, People's Republic of China.
The Institute of Translational Medicine Research, Tianjin Union Medical Center, Nankai Universitygrid.216938.7 Affiliated Hospital, Nankai University, Tianjin, People's Republic of China.
mBio. 2021 Dec 21;12(6):e0269221. doi: 10.1128/mBio.02692-21. Epub 2021 Dec 14.
Many enteropathogenic bacteria express a needle-like type III secretion system (T3SS) that translocates effectors into host cells promoting infection. O antigen (OAg) constitutes the outer layer of Gram-negative bacteria protecting bacteria from host immune responses. constitutively shortens the OAg molecule in its three-dimensional conformation by glucosylation, leading to enhanced T3SS function. However, whether and how other enteropathogenic bacteria shorten the OAg molecule that probably facilitates infection remain unknown. For the first time, we report a smart mechanism by which enterohemorrhagic Escherichia coli specifically reduces the size of the OAg molecule at the infection site upon sensing mechanical signals of intestinal epithelial cell attachment via the membrane protein YgjI. YgjI represses expression of the OAg chain length regulator gene via the global regulator H-NS, leading to shortened OAg chains and injection of more T3SS effectors into host cells. However, bacteria express long-chain OAg in the intestinal lumen benefiting their survival. Animal experiments show that blocking this regulatory pathway significantly attenuates bacterial virulence. This finding enhances our understanding of interactions between the surfaces of bacterial and host cells and the way this interaction enhances bacterial pathogenesis. Little is known about the regulation of cell wall structure of enteropathogenic bacteria within the host. Here, we report that enterohemorrhagic Escherichia coli regulates its cell wall structure during the infection process, which balances its survival in the intestinal lumen and infection of intestinal epithelial cells. In the intestinal lumen, bacteria express long-chain OAg, which is located in the outer part of the cell wall, leading to enhanced resistance to antimicrobial peptides. However, upon epithelial cell attachment, bacteria sense this mechanical signal via a membrane protein and reduce the OAg chain length, resulting in enhanced injection into epithelial cells of T3SS effectors that mediate host cell infection. Similar regulation mechanisms of cell wall structure in response to host cell attachment may be widespread in pathogenic bacteria and closely related with bacterial pathogenesis.
许多肠致病性细菌表达一种针状的 III 型分泌系统（T3SS），该系统将效应蛋白转运到宿主细胞中，促进感染。O 抗原（OAg）构成革兰氏阴性细菌的外层，保护细菌免受宿主免疫反应的影响。在其三维构象中通过葡糖基化使 OAg 分子不断缩短，从而增强 T3SS 功能。然而，其他肠致病性细菌是否以及如何缩短 OAg 分子，从而可能促进感染，目前尚不清楚。我们首次报道了一种聪明的机制，即肠出血性大肠杆菌通过膜蛋白 YgjI 感应肠上皮细胞附着的机械信号，特异性地在感染部位减小 OAg 分子的大小。YgjI 通过全局调控因子 H-NS 抑制 OAg 链长调节剂基因的表达，导致 OAg 链缩短，更多 T3SS 效应蛋白注入宿主细胞。然而，细菌在肠腔中表达长链 OAg，有利于其存活。动物实验表明，阻断这条调控途径可显著降低细菌的毒力。这一发现增强了我们对细菌和宿主细胞表面之间相互作用以及这种相互作用增强细菌发病机制的理解。关于宿主内肠致病性细菌细胞壁结构的调控，我们知之甚少。在这里，我们报告肠出血性大肠杆菌在感染过程中调节其细胞壁结构，这平衡了其在肠腔中的存活和对肠上皮细胞的感染。在肠腔中，细菌表达位于细胞壁外部分的长链 OAg，从而增强了对抗菌肽的抗性。然而，一旦上皮细胞附着，细菌就会通过膜蛋白感应到这种机械信号，并减少 OAg 链长，从而增强 T3SS 效应蛋白注入介导宿主细胞感染的上皮细胞。这种对宿主细胞附着的细胞壁结构的类似调控机制可能在致病性细菌中广泛存在，与细菌发病机制密切相关。
