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首页> 外文期刊>Infection and immunity >Saccharomyces boulardii Protease Inhibits the Effects of Clostridium difficile Toxins A and B in Human Colonic Mucosa
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Saccharomyces boulardii Protease Inhibits the Effects of Clostridium difficile Toxins A and B in Human Colonic Mucosa

机译：酿酒酵母蛋白酶抑制艰难梭菌毒素A和B在人结肠粘膜中的作用

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Saccharomyces boulardii is a nonpathogenic yeast used in the treatment of Clostridium difficile diarrhea and colitis. We have reported that S. boulardii inhibitsC. difficile toxin A enteritis in rats by releasing a 54-kDa protease which digests the toxin A molecule and its brush border membrane (BBM) receptor (I. Castagliuolo, J. T. LaMont, S. T. Nikulasson, and C. Pothoulakis, Infect. Immun. 64:5225–5232, 1996). The aim of this study was to further evaluate the role of S. boulardii protease in preventing C. difficile toxin A enteritis in rat ileum and determine whether it protects human colonic mucosa from C. difficile toxins. A polyclonal rabbit antiserum raised against purified S. boulardii serine protease inhibited by 73% the proteolytic activity present in S. boulardii conditioned medium in vitro. The anti-protease immunoglobulin G (IgG) prevented the action of S. boulardiion toxin A-induced intestinal secretion and mucosal permeability to [3H]mannitol in rat ileal loops, while control rabbit IgG had no effect. The anti-protease IgG also prevented the effects ofS. boulardii protease on digestion of toxins A and B and on binding of [3H]toxin A and [3H]toxin B to purified human colonic BBM. Purified S. boulardii protease reversed toxin A- and toxin B-induced inhibition of protein synthesis in human colonic (HT-29) cells. Furthermore, toxin A- and B-induced drops in transepithelial resistance in human colonic mucosa mounted in Ussing chambers were reversed by 60 and 68%, respectively, by preexposing the toxins to S. boulardii protease. We conclude that the protective effects of S. boulardii onC. difficile-induced inflammatory diarrhea in humans are due, at least in part, to proteolytic digestion of toxin A and B molecules by a secreted protease.
机译： Saccharomyces boulardii 是一种非致病性酵母，用于治疗艰难梭菌（Clostridium difficile）腹泻和结肠炎。我们已经报告了 S。 boulardii 抑制 C。通过释放一种54kDa的蛋白酶来消化大鼠A艰难梭菌毒素A肠炎，该蛋白酶可消化毒素A分子及其刷状缘膜（BBM）受体（I. Castagliuolo，JT LaMont，ST Nikulasson和C.Pothoulakis，Infect。 Immun。64：5225-5232，1996）。这项研究的目的是进一步评估 S的作用。 boulardii 蛋白酶预防 C。大鼠回肠中的艰难梭菌毒素A肠炎，并确定其是否保护人结肠粘膜免受 C侵害。难消化毒素。产生了针对纯化的 S的多克隆兔抗血清。 boulardii 丝氨酸蛋白酶抑制 S中存在的蛋白水解活性73％。 boulardii条件培养液。抗蛋白酶免疫球蛋白G（IgG）阻止了 S的作用。乙醛对大鼠回肠induced中毒素A诱导的肠道分泌和对[ 3 H]甘露醇的黏膜通透性的影响，而对照兔IgG无作用。抗蛋白酶IgG也预防了em的作用。 boulardii 蛋白酶对毒素A和B的消化以及[ 3 H]毒素A和[ 3 H]毒素B与纯化的人结肠BBM结合的影响。纯化的 S。 boulardii蛋白酶可逆转毒素A和毒素B对人结肠（HT-29）细胞蛋白质合成的抑制作用。此外，通过将毒素预先暴露于 S，毒素A和B诱导的安装在Ussings室中的人结肠粘膜的经上皮阻力下降分别逆转了60％和68％。 boulardii 蛋白酶。我们得出结论， S具有保护作用。 boulardii 在 C上。艰难梭菌引起的人类炎性腹泻至少部分是由于分泌的蛋白酶对毒素A和B分子的蛋白水解消化所致。

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