Higashi Dustin L, Lee Shaun W, Snyder Aurelie, Weyand Nathan J, Bakke Antony, So Magdalene
Department of Molecular Microbiology and Immunology, Oregon Health and Science University, 3181 SW Sam Jackson Park Rd., Portland, Oregon 97239, USA.
Infect Immun. 2007 Oct;75(10):4743-53. doi: 10.1128/IAI.00687-07. Epub 2007 Aug 6.
Neisseria gonorrhoeae is the bacterium that causes gonorrhea, a major sexually transmitted disease and a significant cofactor for human immunodeficiency virus transmission. The retactile N. gonorrhoeae type IV pilus (Tfp) mediates twitching motility and attachment. Using live-cell microscopy, we reveal for the first time the dynamics of twitching motility by N. gonorrhoeae in its natural environment, human epithelial cells. Bacteria aggregate into microcolonies on the cell surface and induce a massive remodeling of the microvillus architecture. Surprisingly, the microcolonies are motile, and they fuse to form progressively larger structures that undergo rapid reorganization, suggesting that bacteria communicate with each other during infection. As reported, actin plaques form beneath microcolonies. Here, we show that cortical plaques comigrate with motile microcolonies. These activities are dependent on pilT, the Tfp retraction locus. Cultures infected with a pilT mutant have significantly higher numbers of apoptotic cells than cultures infected with the wild-type strain. Inducing pilT expression with isopropyl-beta-D-thiogalactopyranoside partially rescues cells from infection-induced apoptosis, demonstrating that Tfp retraction is intrinsically cytoprotective for the host. Tfp-mediated attachment is therefore a continuum of microcolony motility and force stimulation of host cell signaling, leading to a cytoprotective effect.
淋病奈瑟菌是引起淋病的细菌,淋病是一种主要的性传播疾病,也是人类免疫缺陷病毒传播的重要辅助因素。可收缩的淋病奈瑟菌IV型菌毛(Tfp)介导了颤动运动和附着。通过活细胞显微镜观察,我们首次揭示了淋病奈瑟菌在其自然环境即人类上皮细胞中的颤动运动动态。细菌在细胞表面聚集形成微菌落,并诱导微绒毛结构发生大规模重塑。令人惊讶的是,微菌落是可移动的,它们融合形成逐渐更大的结构,这些结构会经历快速重组,这表明细菌在感染过程中相互交流。如报道的那样,肌动蛋白斑块在微菌落下方形成。在这里,我们表明皮质斑块与可移动的微菌落一起迁移。这些活动依赖于pilT,即Tfp收缩位点。用pilT突变体感染的培养物中凋亡细胞的数量明显高于用野生型菌株感染的培养物。用异丙基-β-D-硫代半乳糖苷诱导pilT表达可部分挽救细胞免受感染诱导的凋亡,这表明Tfp收缩对宿主具有内在的细胞保护作用。因此,Tfp介导的附着是微菌落运动和对宿主细胞信号传导的力刺激的连续过程,从而导致细胞保护作用。