The N. gonorrhoeae Type IV Pilus Stimulates Mechanosensitive Pathways and Cytoprotection through a pilT-Dependent Mechanism

The Neisseria gonorrhoeae type IV pilus is a retractile appendage that can generate forces near 100 pN. We tested the hypothesis that type IV pilus retraction influences epithelial cell gene expression by exerting tension on the host membrane. Wild-type and retraction-defective bacteria altered the expression of an identical set of epithelial cell genes during attachment. Interestingly, pilus retraction, per se, did not regulate novel gene expression but, rather, enhanced the expression of a subset of the infection-regulated genes. This is accomplished through mitogen-activated protein kinase activation and at least one other undefined stress-activated pathway. These results can be reproduced by applying artificial force on the epithelial membrane, using a magnet and magnetic beads. Importantly, this retraction-mediated signaling increases the ability of the cell to withstand apoptotic signals triggered by infection. We conclude that pilus retraction stimulates mechanosensitive pathways that enhance the expression of stress-responsive genes and activate cytoprotective signaling. A model for the role of pilus retraction in influencing host cell survival is presented.淋病奈瑟菌（Neisseria gonorrhoeae）IV型菌毛（type IV pilus）是一种可收缩的附属结构，可产生近100皮牛（pN）的作用力。我们验证了如下假说：IV型菌毛收缩可通过对宿主细胞膜施加张力，进而影响上皮细胞的基因表达。在细菌黏附宿主细胞的过程中，野生型菌株与收缩缺陷型细菌均可改变同一组上皮细胞基因的表达水平。值得注意的是，菌毛收缩本身并不会调控新的基因表达，而是仅增强感染调控基因子集的表达。这一效应通过丝裂原活化蛋白激酶（mitogen-activated protein kinase）的激活，以及至少一条尚未阐明的应激激活通路得以实现。利用磁体与磁珠对上皮细胞膜施加人工张力，即可复现上述实验结果。尤为重要的是，这种由菌毛收缩介导的信号通路可增强细胞抵御感染触发的凋亡信号的能力。综上，我们认为菌毛收缩可激活机械敏感通路，该通路既能增强应激响应基因的表达，又能启动细胞保护性信号转导。本文还提出了菌毛收缩在调控宿主细胞存活过程中作用的相关模型。