Neisseria gonorrhoeae, a Gram-negative obligate human pathogenic bacterium, infects human epithelial cells and causes sexually transmitted diseases. Emerging multi-antibiotic resistant gonococci and increasing numbers of infections complicate the treatment of infected patients. Here, we used an shRNA library screen and next-generation sequencing to identify factors involved in epithelial cell infection. Folliculin (FLCN), a 64 kDa protein with a tumor repressor function was identified as a novel host factor important for N. gonorrhoeae survival after uptake. We further determined that FLCN did not affect N. gonorrhoeae adherence and invasion but was essential for its survival in the cells by modulating autophagy. In addition, FLCN was also required to maintain cell to cell contacts in the epithelial layer. In an infection model with polarized cells, FLCN inhibited the polarized localization of E-cadherin and the transcytosis of gonococci across polarized epithelial cells. In conclusion, we demonstrate here the connection between FLCN and bacterial infection and in particular the role of FLCN in the intracellular survival and transcytosis of gonococci across polarized epithelial cell layers.

淋球菌革兰氏阴性专性人类致病菌可感染人类上皮细胞并引起性传播疾病。新兴的多抗生素耐药性淋球菌和越来越多的感染使感染患者的治疗复杂化。在这里，我们使用了一个shRNA文库筛选和下一代测序来鉴定参与上皮细胞感染的因素。Folliculin（FLCN）是一种具有肿瘤阻遏功能的64 kDa蛋白，被认为是对淋病奈瑟菌摄取后的存活率。我们进一步确定FLCN不会影响淋病奈瑟菌粘附和侵袭，但通过调节自噬对细胞在细胞中的存活至关重要。另外，还需要FLCN来维持上皮层中的细胞间接触。在具有极化细胞的感染模型中，FLCN抑制了E-钙粘蛋白的极化定位和淋球菌跨极化上皮细胞的转胞吞作用。总之，我们在这里证明FLCN与细菌感染之间的联系，尤其是FLCN在淋球菌跨极化上皮细胞层的细胞内存活和转胞吞作用中的作用。