Dual membrane-spanning anti-sigma factors regulate vesiculation in Bacteroides thetaiotaomicron.
Dual membrane-spanning anti-sigma factors regulate vesiculation in Bacteroides thetaiotaomicron.
复制标题
双跨膜抗σ因子调节多形拟杆菌中的囊泡形成。
DOI：
10.1073/pnas.2321910121
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发表时间：
2024
影响因子：
11.1
通讯作者：
Feldman,MarioF
中科院分区：
文献类型：
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作者：
Pardue,EvanJ;Sartorio,MarianaG;Jana,Biswanath;Scott,NichollasE;Beatty,WandyL;Ortiz-Marquez,JuanC;VanOpijnen,Tim;Hsu,Fong-Fu;Potter,RobertF;Feldman,MarioF
拟杆菌门是人类肠道微生物群的丰富成员，通过调节宿主免疫力和降解膳食和宿主来源的聚糖来塑造肠道景观。这些过程部分由外膜囊泡（OMV）介导。在这里，我们开发了一个高通量筛选，以确定所需的基因OMV生物合成和调节多形拟杆菌（Bt）。我们鉴定了一个控制OMV生物发生的跨双膜抗σ因子（Dma）家族。我们进行了分子和多组学分析，以证明Dma家族的创始成员Dma 1的缺失通过控制ECF21家族σ因子Das 1及其下游调节子的活性来调节OMV的产生。Dma1具有以前未表征的结构域组织，使Dma1能够跨越Bt的内膜和外膜。系统发育分析表明，这一共同特征的DMA家庭是有限的拟杆菌门。这项研究为人类肠道细菌中OMV生物合成的调节提供了机制见解。
Bacteroidota are abundant members of the human gut microbiota that shape the enteric landscape by modulating host immunity and degrading dietary- and host-derived glycans. These processes are mediated in part byOuterMembraneVesicles (OMVs). Here, we developed a high-throughput screen to identify genes required for OMV biogenesis and its regulation inBacteroides thetaiotaomicron(Bt). We identified a family ofDualmembrane-spanninganti-sigma factors (Dma) that control OMV biogenesis. We conducted molecular and multiomic analyses to demonstrate that deletion of Dma1, the founding member of the Dma family, modulates OMV production by controlling the activity of the ECF21 family sigma factor, Das1, and its downstream regulon. Dma1 has a previously uncharacterized domain organization that enables Dma1 to span both the inner and outer membrane ofBt. Phylogenetic analyses reveal that this common feature of the Dma family is restricted to the phylum Bacteroidota. This study provides mechanistic insights into the regulation of OMV biogenesis in human gut bacteria.