Wei Lifan, Qiao Haoxian, Sit Brandon, Yin Kaiyu, Yang Guanhua, Ma Ruiqing, Ma Jiabao, Yang Chun, Yao Jun, Ma Yue, Xiao Jingfan, Liu Xiaohong, Zhang Yuanxing, Waldor Matthew K, Wang Qiyao
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China.
Division of Infectious Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
iScience. 2019 Oct 25;20:310-323. doi: 10.1016/j.isci.2019.09.028. Epub 2019 Sep 25.
Bacterial pathogens are thought to activate expression of virulence genes upon detection of host-associated cues, but identification of the nature of such signals has proved difficult. We generated a genome-scale defined transposon mutant library in Edwardsiella piscicida, an important fish pathogen, to quantify the fitness of insertion mutants for intracellular growth in macrophages and in turbot (Scophthalmus maximus). These screens identified EvrA, a transcription activator that induces expression of esrB, a key virulence regulator. EvrA is directly bound and activated by mannose-6-phosphate (man-6P) derived from actively imported mannose. Mutants lacking EvrA or expressing an EvrA unable to bind man-6P were similarly attenuated in turbot. Exogenously added mannose promoted E. piscicida virulence, and high levels of mannose were detected in fish tissue. Together, these observations reveal that binding of a host-derived sugar to a transcription factor can facilitate pathogen sensing of the host environment and trigger virulence programs.
人们认为细菌病原体在检测到宿主相关信号后会激活毒力基因的表达，但事实证明，确定此类信号的性质很困难。我们在重要的鱼类病原体杀鲑气单胞菌爱德华氏菌中构建了一个全基因组规模的定义转座子突变体文库，以量化插入突变体在巨噬细胞和大菱鲆（Scophthalmus maximus）细胞内生长的适应性。这些筛选鉴定出了EvrA，一种诱导关键毒力调节因子esrB表达的转录激活因子。EvrA直接被主动摄取的甘露糖衍生的6-磷酸甘露糖（man-6P）结合并激活。缺乏EvrA或表达无法结合man-6P的EvrA的突变体在大菱鲆中同样减毒。外源添加的甘露糖促进了杀鲑气单胞菌的毒力，并且在鱼类组织中检测到了高水平的甘露糖。总之，这些观察结果表明，宿主来源的糖类与转录因子的结合可以促进病原体对宿主环境的感知并触发毒力程序。
