Zhong Xiaojun, Liu Fuwen, Liang Tianqi, Lu Ranran, Shi Mengting, Zhou Xiujuan, Yang Menghua
College of Animal Science and Technology, College of Veterinary Medicine, Zhejiang A & F University, Key Laboratory of Applied Technology on Green-Eco-Healthy Animal Husbandry of Zhejiang Province, Zhejiang Provincial Engineering Laboratory for Animal Health Inspection & Internet Technology, Hangzhou, China.
PLoS Pathog. 2024 Jul 22;20(7):e1012410. doi: 10.1371/journal.ppat.1012410. eCollection 2024 Jul.
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.
肠道病原体面临的最大挑战之一是应对宿主中营养物质可用性的快速变化。然而，病原体感知胃肠道信号并利用宿主可用营养物质进行增殖的机制在很大程度上仍不清楚。在这里，我们在副溶血性弧菌中鉴定了一个双组分系统TtrRS，它能感知环境中的连四硫酸盐，并随后激活ttrRS-ttrBCA-tsdBA基因簇的转录，以促进副溶血性弧菌在成年小鼠中的定殖。我们证明，TsdBA赋予了硫代硫酸盐氧化产生连四硫酸盐的能力，而连四硫酸盐可被TtrRS感知。TtrRS自我调节并直接激活ttrBCA和tsdBA基因簇的转录。激活的TtrBCA通过诱导连四硫酸盐和硫代硫酸盐的还原，在微需氧条件下促进细菌生长。TtrRS对TtrBCA和TsdBA的激活对于副溶血性弧菌在成年小鼠中的定殖很重要。因此，TtrRS及其靶基因构成了一个连四硫酸盐响应遗传回路，以利用宿主可用的硫化合物，这进一步促进了副溶血性弧菌在肠道中的定殖。
