Bacteroides fragilis toxin expression enables lamina propria niche acquisition in the developing mouse gut.
Bacteroides fragilis toxin expression enables lamina propria niche acquisition in the developing mouse gut.
复制标题
脆弱拟杆菌毒素的表达能够在发育中的小鼠肠道中获得固有层生态位。
DOI：
10.1038/s41564-023-01559-9
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发表时间：
2024
影响因子：
28.3
通讯作者：
BubeckWardenburg,Juliane
中科院分区：
文献类型：
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作者：
Hill,CraigA;Casterline,BenjaminW;Valguarnera,Ezequiel;Hecht,AaronL;Shepherd,ElizabethStanley;Sonnenburg,JustinL;BubeckWardenburg,Juliane
细菌毒素是经过充分研究的毒力因子；然而，最近的研究揭示了它们在细菌生态位适应中的重要性。产肠毒素脆弱拟杆菌 (ETBF) 表达 B.我们假设脆弱毒素（BFT）可能会导致结肠上皮损伤和生态位获得。我们开发了小鼠体内 ETBF 的垂直传播模型，表明 BFT 使 ETBF 在结肠微生物组发育过程中能够进入固有层 (LP) 生态位，而非产毒 B 无法进入。脆弱。 ETBF 进入 LP 需要 BFT 金属蛋白酶活性，并且显示出断奶前的时间限制，具体取决于杯状细胞相关的传代。原位单细胞分析显示bft在顶端上皮表面和LP内表达。 BFT 表达增加杯状细胞数量和杯状细胞相关传代形成。这些发现定义了细菌毒素表达指定发育生态位获取的范例，表明毒素赋予的选择性优势可能会影响长期宿主健康。
Bacterial toxins are well-studied virulence factors; however, recent studies have revealed their importance in bacterial niche adaptation. EnterotoxigenicBacteroides fragilis(ETBF) expressesB. fragilistoxin (BFT) that we hypothesized may contribute to both colonic epithelial injury and niche acquisition. We developed a vertical transmission model for ETBF in mice that showed that BFT enabled ETBF to access a lamina propria (LP) niche during colonic microbiome development that was inaccessible to non-toxigenicB. fragilis. LP entry by ETBF required BFT metalloprotease activity, and showed temporal restriction to the pre-weaning period, dependent on goblet-cell-associated passages. In situ single-cell analysis showedbftexpression at the apical epithelial surface and within the LP. BFT expression increased goblet cell number and goblet-cell-associated passage formation. These findings define a paradigm by which bacterial toxin expression specifies developmental niche acquisition, suggesting that a selective advantage conferred by a toxin may impact long-term host health.