Nestlé Research, Lausanne, Switzerland.
Host-Microbe Interactomics Group, Wageningen University and Research, De Elst 1, 6708 WD, Wageningen, The Netherlands.
Sci Rep. 2021 Mar 31;11(1):7236. doi: 10.1038/s41598-021-86740-y.
The Serine Protease Inhibitor (serpin) protein has been suggested to play a key role in the interaction of bifidobacteria with the host. By inhibiting intestinal serine proteases, it might allow bifidobacteria to reside in specific gut niches. In inflammatory diseases where serine proteases contribute to the innate defense mechanism of the host, serpin may dampen the damaging effects of inflammation. In view of the beneficial roles of this protein, it is important to understand how its production is regulated. Here we demonstrate that Bifidobacterium longum NCC 2705 serpin production is tightly regulated by carbohydrates. Galactose and fructose increase the production of this protein while glucose prevents it, suggesting the involvement of catabolite repression. We identified that di- and oligosaccharides containing galactose (GOS) and fructose (FOS) moieties, including the human milk oligosaccharide Lacto-N-tetraose (LNT), are able to activate serpin production. Moreover, we show that the carbohydrate mediated regulation is conserved within B. longum subsp. longum strains but not in other bifidobacterial taxons harboring the serpin coding gene, highlighting that the serpin regulation circuits are not only species- but also subspecies- specific. Our work demonstrates that environmental conditions can modulate expression of an important effector molecule of B. longum, having potential important implications for probiotic manufacturing and supporting the postulated role of serpin in the ability of bifidobacteria to colonize the intestinal tract.
丝氨酸蛋白酶抑制剂（serpin）蛋白被认为在双歧杆菌与宿主相互作用中发挥关键作用。通过抑制肠道丝氨酸蛋白酶，它可能允许双歧杆菌存在于特定的肠道生态位。在丝氨酸蛋白酶有助于宿主先天防御机制的炎症性疾病中，丝氨酸蛋白酶抑制剂可能会减轻炎症的破坏性影响。鉴于该蛋白的有益作用，了解其产生如何受到调控非常重要。在这里，我们证明长双歧杆菌 NCC 2705 丝氨酸蛋白酶抑制剂的产生受到碳水化合物的严格调控。半乳糖和果糖会增加这种蛋白质的产生，而葡萄糖则会阻止其产生，这表明存在分解代谢物阻遏作用。我们发现含有半乳糖（GOS）和果糖（FOS）部分的二糖和寡糖（如人乳寡糖 Lacto-N-tetraose（LNT））能够激活丝氨酸蛋白酶抑制剂的产生。此外，我们表明，碳水化合物介导的调控在长双歧杆菌亚种内是保守的，但在其他含有丝氨酸蛋白酶编码基因的双歧杆菌分类群中则不是，这表明丝氨酸蛋白酶抑制剂调控回路不仅具有种特异性，而且具有亚种特异性。我们的工作表明，环境条件可以调节长双歧杆菌重要效应分子的表达，这对益生菌的制造具有潜在的重要意义，并支持丝氨酸蛋白酶抑制剂在双歧杆菌定植肠道能力中的假定作用。
