Toxins, butyric acid, and other short-chain fatty acids are coordinately expressed and down-regulated by cysteine in Clostridium difficile
Toxins, butyric acid, and other short-chain fatty acids are coordinately expressed and down-regulated by cysteine in Clostridium difficile
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DOI：
10.1128/iai.68.10.5881-5888.2000
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发表时间：
2000-10-01
影响因子：
3.1
通讯作者：
Åkerlund, T
中科院分区：
文献类型：
--
作者：
Karlsson, S;Lindberg, A;Åkerlund, T
最近发现，当将九种氨基酸的混合物添加到VPI 10463菌株的蛋白酵母膏(PY)培养中时，其抑制艰难梭菌毒素的产生(S.Karlsson，L.G.Burman和T.Akerlund，Microbiical145：1683-1693,1999)。在本研究中，发现其中7种氨基酸对艰难梭菌的参考菌株(n=6)和临床分离株(n=28)的毒素产生有中等程度的抑制作用，而脯氨酸和半胱氨酸对艰难梭菌的影响最大(半胱氨酸对艰难梭菌的抑制率为99%)。此外，半胱氨酸的衍生物，如乙酰半胱氨酸、谷胱甘肽和半胱氨酸有效地下调毒素的表达。半胱氨酸和半胱氨酸对毒素产量的影响表明，毒素的表达不受氧化还原电位的调节。几种代谢途径，包括丁酸和丁醇的产生，与PY中的毒素共同诱导，并被半胱氨酸下调。3-羟基丁酰辅酶A脱氢酶是乙酰丁酸梭菌溶剂化过程中的关键酶，也是产毒最高的蛋白质之一。在不同的生长条件下，添加丁酸均可诱导产毒，而添加丁醇则相反。结果表明艰难梭菌的特定代谢过程和毒素表达之间存在耦合，某些氨基酸可以协调地改变这些途径。我们推测，通过给结肠注射这种氨基酸来下调毒素的产生，可能成为预防和治疗艰难梭菌相关性腹泻的一种新方法。
Its was recently found that a mixture of nine amino acids down-regulate Clostridium difficile toxin production when added to peptone yeast extract (PY) cultures of strain VPI 10463 (S. Karlsson, L. G. Burman, and T. Akerlund, Microbiology 145:1683-1693, 1999). In the present study, seven of these amino acids were found to exhibit a moderate suppression of toxin production, whereas proline and particularly cysteine had the greatest impact, on both reference strains (n = 6) and clinical isolates (n = 28) of C. difficile (>99% suppression by cysteine in the highest toxin-producing strain). Also, cysteine derivatives such as acetylcysteine, glutathione, and cystine effectively down-regulated toxin expression. An impact of both cysteine and cystine but not of thioglycolate on toxin yield indicated that toxin expression was not regulated by the oxidation-reduction potential. Several metabolic pathways, including butyric acid and butanol production, were coinduced with the toxins in PY and down-regulated by cysteine. The enzyme 3-hydroxybutyryl coenzyme A dehydrogenase, a key enzyme in solventogenesis in Clostridium acetobutylicum, was among the most up-regulated proteins during high toxin production. The addition of butyric acid to various growth media induced toxin production, whereas the addition of butanol had the opposite effect. The results indicate a coupling between specific metabolic processes and toxin expression in C. difficile and that certain amino acids can alter these pathways coordinately. We speculate that down-regulation of toxin production by the administration of such amino acids to the colon may become a novel approach to prophylaxis and therapy for C. difficile-associated diarrhea.