Quorum sensing-activated phenylalanine metabolism drives OMV biogenesis to enhance mosquito commensal colonization resistance to Plasmodium.

Quorum sensing-activated phenylalanine metabolism drives OMV biogenesis to enhance mosquito commensal colonization resistance to Plasmodium.
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DOI:
10.1016/j.chom.2023.08.017
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发表时间:
2023-09
影响因子:
30.3
通讯作者:
Yongmao Jiang;Han Gao;Lihua Wang;Wenqian Hu;Guandong Wang;Siwei Wang
Yongmao Jiang;Han Gao;Lihua Wang;Wenqian Hu;Guandong Wang;Siwei Wang
中科院分区:
医学1区
文献类型:
--
作者:
Yongmao Jiang;Han Gao;Lihua Wang;Wenqian Hu;Guandong Wang;Siwei Wang

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肠道菌群及其与宿主的共生关系对预防病原体感染至关重要。然而,关于驱动共生殖民化的机制知之甚少。通常在按蚊中发现的沙雷杆菌,可能介导蚊子对疟原虫的抗性。UsingS。以uilyticasu_yn1为模型,我们发现群体感应(quorum sensing, QS)电路对稳定定植至关重要。摄取血液后,QS合成酶SueI产生信号分子n -己醇- l-高丝氨酸内酯(C6-HSL)。一旦C6-HSL与QS受体SueR结合,苯丙氨酸-乙酰辅酶A (CoA)转化途径的抑制被解除。该途径调节外膜囊泡(OMV)的生物发生,促进锯齿状生物膜样聚集体的形成,促进肠道适应和定植。值得注意的是,将携带serratias_yn1的按蚊暴露于C6-HSL中增加了serratias_yn1的定植并增强了疟原虫的传播阻断效果。这些发现为OMV的生物发生和共生肠道定植提供了见解,并确定了增强共生病原体抗性的有力策略。
Gut microbiota and its symbiotic relationship with the host are crucial for preventing pathogen infection. However, little is known about the mechanisms that drive commensal colonization.Serratiabacteria, commonly found inAnophelesmosquitoes, potentially mediate mosquito resistance toPlasmodium. UsingS. ureilyticaSu_YN1 as a model, we show that a quorum sensing (QS) circuit is crucial for stable colonization. After blood ingestion, the QS synthase SueI generates the signaling molecule N-hexanoyl-L-homoserine lactone (C6-HSL). Once C6-HSL binds to the QS receptor SueR, repression of the phenylalanine-to-acetyl-coenzyme A (CoA) conversion pathway is lifted. This pathway regulates outer membrane vesicle (OMV) biogenesis and promotesSerratiabiofilm-like aggregate formation, facilitating gut adaptation and colonization. Notably, exposingSerratiaSu_YN1-carryingAnophelesmosquitoes to C6-HSL increasesSerratiagut colonization and enhancesPlasmodiumtransmission-blocking efficacy. These findings provide insights into OMV biogenesis and commensal gut colonization and identify a powerful strategy for enhancing commensal resistance to pathogens.