Abstract:
One of the greatest challenges encountered by enteric pathogens is responding to rapid changes of nutrient availability in host. However, the mechanisms by which pathogens sense gastrointestinal signals and exploit available host nutrients for proliferation remain largely unknown. Here, we identified a two-component system in Vibrio parahaemolyticus, TtrRS, which senses environmental tetrathionate and subsequently activates the transcription of the ttrRS-ttrBCA-tsdBA gene cluster to promote V. parahaemolyticus colonization of adult mice. We demonstrated that TsdBA confers the ability of thiosulfate oxidation to produce tetrathionate which is sensed by TtrRS. TtrRS autoregulates and directly activates the transcription of the ttrBCA and tsdBA gene clusters. Activated TtrBCA promotes bacterial growth under micro-aerobic conditions by inducing the reduction of both tetrathionate and thiosulfate. TtrBCA and TsdBA activation by TtrRS is important for V. parahaemolyticus to colonize adult mice. Therefore, TtrRS and their target genes constitute a tetrathionate-responsive genetic circuit to exploit the host available sulfur compounds, which further contributes to the intestinal colonization of V. parahaemolyticus.
摘要:
肠道病原体遇到的最大挑战之一是对宿主中营养可用性的快速变化做出反应。然而,病原体感知胃肠道信号并利用可用宿主营养进行增殖的机制仍然未知。这里,我们在副溶血性弧菌中发现了一个双组分系统,TtrRS,它感应环境四硫酸盐,随后激活ttrRS-ttrBCA-tsdBA基因簇的转录,以促进成年小鼠的副溶血弧菌定植。我们证明了TsdBA赋予硫代硫酸盐氧化产生四硫酸盐的能力,该能力可由TtrRS感知。TtrRS自动调节并直接激活ttrBCA和tsdBA基因簇的转录。活化的TtrBCA通过诱导四硫酸盐和硫代硫酸盐的还原来促进微氧条件下的细菌生长。通过TtrRS激活TtrBCA和TsdBA对于副溶血弧菌在成年小鼠定植是重要的。因此,TtrRS和它们的靶基因构成了一个四硫氨酸反应遗传回路,以利用宿主可用的硫化合物,这进一步有助于副溶血性弧菌的肠道定植。