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唾液乳杆菌胆盐胁迫应激机制研究进展
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摘要
唾液乳杆菌是人体肠道原籍菌,具有调节肠道菌群、增强机体免疫和预防肠道炎症等益生功效。肠道内的胆盐具有杀菌作用,能够破坏细菌的细胞膜,进而引起蛋白质错误折叠和DNA氧化损伤等危害。因此,能够耐受胆盐胁迫是唾液乳杆菌在肠道内生存和发挥益生作用的前提。研究表明,唾液乳杆菌主要通过以下机制应对胆盐胁迫。(1)增强表面屏障:细胞表面正电荷的修饰及特定表面蛋白的富集,阻止胆盐向胞内入侵;(2)胆盐外排作用:ABC家族跨膜转运系统介导胆盐的泵出,减少胞内胆盐积累;(3)加强修复机制:通过提高氧化还原酶和分子伴侣蛋白的合成,应对胆盐造成的氧化损伤和蛋白变性;(4)调整中心代谢途径:主要通过加速麦芽糖和甘油等碳源的代谢,为细胞提供能量和还原力;(5)启动转录调控系统:通过转录因子响应胆盐信号调控生理进程,提高胆盐胁迫耐受性。唾液乳杆菌胆盐响应分子机制的研究为揭示其肠道适应性提供了新的理论依据。
Lactobacillussalivarius is a member of the indigenous microbiota of the human gastrointestinal tract(GIT),and a variety of probiotic properties have been proposed for some strains,such as the ability to modulate gut microbiota,stimulate protective immune response and attenuate gastrointestinal inflammation.Bilesalts are detergent-like biological compounds with strongantimicrobial activities that disrupt cell membrane,induce protein misfolding and causeoxidative damage toDNA.Therefore,tolerance to bile stress is critical for L.salivarius to survive and exert beneficial effects in the GIT.Recentstudies on the bile stress responsein L.salivariusrevealed the following main mechanismsresponsible for counteracting bile toxicity;(i)strengthening the barrier property of cell envelope to prevent bile adsorption,(ii) active extrusion of bile salt through ABC transporters to reduce its intracellular accumulation,(iii) improving the production of oxidoreductases and chaperones to counteract the oxidative stress and protein misfolding effects caused by bile,(iv) altering central metabolism pathways mainly by increase the utilization of maltose and glycerol to enhance the generation of ATP and reducing equivalents,and(v) activating transcription factors which could sense bile stress signals and regulate cellular processesaccordingly,thus improving bile tolerance.These results provide a new insight into the molecular mechanisms that enable L.salivariuslo cope with bile stress and survive in the GIT.
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