Department of Molecular Microbiology, Washington University School of Medicine, Saint Louis, MO 63110.
Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, VIC 3000, Australia.
Proc Natl Acad Sci U S A. 2024 Mar 5;121(10):e2321910121. doi: 10.1073/pnas.2321910121. Epub 2024 Feb 29.
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 by uter embrane esicles (OMVs). Here, we developed a high-throughput screen to identify genes required for OMV biogenesis and its regulation in (). We identified a family of ual embrane-spanning nti-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 of . 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.
拟杆菌门是人类肠道微生物群中的丰富成员，通过调节宿主免疫和降解饮食和宿主来源的聚糖来塑造肠道景观。这些过程部分是由 （）的 （）介导的。在这里，我们开发了一种高通量筛选方法，以鉴定 （）中 OMV 生物发生及其调控所需的基因。我们鉴定了一类跨膜抗西格玛因子家族（Dma），它们控制 OMV 的生物发生。我们进行了分子和多组学分析，以证明 Dma 家族的创始成员 Dma1 的缺失通过控制 ECF21 家族西格玛因子 Das1 及其下游调控子的活性来调节 OMV 的产生。Dma1 具有以前未表征的结构域组织，使 Dma1 能够跨越 （）的内外膜。系统发育分析表明，Dma 家族的这一共同特征仅限于拟杆菌门。这项研究为人类肠道细菌中 OMV 生物发生的调控提供了机制上的见解。
