APC Microbiome Ireland, National University of Ireland, Western Road, Cork, Ireland.
School of Microbiology, National University of Ireland, Western Road, Cork, Ireland.
Mol Microbiol. 2019 Jan;111(1):287-301. doi: 10.1111/mmi.14155. Epub 2018 Dec 2.
Development of the human gut microbiota commences at birth, with certain bifidobacterial species representing dominant and early colonisers of the newborn gastrointestinal tract. The molecular basis of Bifidobacterium colonisation, persistence and presumed communication with the host has remained obscure. We previously identified tight adherence (Tad) pili from Bifidobacterium breve UCC2003 as an essential colonisation factor. Here, we demonstrate that bifidobacterial Tad pili also promote in vivo colonic epithelial proliferation. A significant increase in cell proliferation was detectable 5 days postadministration of B. breve UCC2003. Using advanced functional genomic approaches, bacterial strains either (a) producing the Tad pili or (b) lacking the TadE or TadF pseudopilins were created. Analysis of the ability of these mutant strains to promote epithelial cell proliferation in vivo demonstrated that the pilin subunit, TadE, is the bifidobacterial molecule responsible for this proliferation response. These findings were confirmed in vitro using purified TadE protein. Our data imply that bifidobacterial Tad pili may contribute to the maturation of the naïve gut in early life through the production of a specific scaffold of extracellular protein structures, which stimulate growth of the neonatal mucosa.
人类肠道微生物群的发展始于出生，某些双歧杆菌物种是新生儿胃肠道的主要和早期定植者。双歧杆菌定植、持续存在和与宿主假定的交流的分子基础仍然不清楚。我们之前从短双歧杆菌 UCC2003 中鉴定出紧密粘附（Tad）菌毛是一种必需的定植因子。在这里，我们证明双歧杆菌 Tad 菌毛也促进体内结肠上皮细胞增殖。在给予短双歧杆菌 UCC2003 后 5 天，可检测到细胞增殖的显著增加。使用先进的功能基因组方法，创建了（a）产生 Tad 菌毛或（b）缺乏 TadE 或 TadF 假菌毛的细菌株。分析这些突变株在体内促进上皮细胞增殖的能力表明，菌毛亚基 TadE 是负责这种增殖反应的双歧杆菌分子。在体外使用纯化的 TadE 蛋白进行了这些发现的验证。我们的数据表明，双歧杆菌 Tad 菌毛可能通过产生刺激新生儿黏膜生长的特定细胞外蛋白结构支架，为早期生命中幼稚肠道的成熟做出贡献。
