Cyclic AMP and its receptor protein negatively regulate the coordinate expression of cholera toxin and toxin-coregulated pilus in Vibrio cholerae
Cyclic AMP and its receptor protein negatively regulate the coordinate expression of cholera toxin and toxin-coregulated pilus in Vibrio cholerae
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DOI：
10.1073/pnas.94.1.265
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发表时间：
1997-01-07
影响因子：
11.1
通讯作者：
Taylor, RK
中科院分区：
文献类型：
--
作者：
Skorupski, K;Taylor, RK
霍乱弧菌两个基因cyA和CRP的插入突变分别编码腺苷环化酶和环磷酸腺苷(CAMP)受体蛋白(CRP)，在37℃的不允许温度下抑制了霍乱毒素(CT)染色体启动子-LacZ融合的表达。在经典生物型菌株O395中，在各种通常不允许表达的生长条件下，CRP突变在体外增加了CT和毒素共调节菌毛(TCP)的产量。在30℃、pH 8.5的Luria-Bertani(Luria-Bertani)(Luria-Bertani，Luria-Bertani，将CRP突变整合到El Tor菌株C6706中，可以在30℃、pH 6.5的LB介质中生产这些蛋白质。在婴儿小鼠霍乱模型中，与野生型菌株相比，CRP突变使这两种生物型的定植减少了至少100倍。本文提供的数据提示了一种模型，在该模型中，cAMP-CRP在某些环境条件下负面调节经典和El Tor生物型中CT和TCP的表达，并通过调节体内最佳生长所需的其他过程来影响发病机制。
Insertion mutations in two Vibrio cholerae genes, cya and crp, which encode adenylate cyclase and the cyclic AMP (cAMP) receptor protein (CRP), respectively, derepressed the expression of a chromosomal cholera toxin (CT) promoter-lacZ fusion at the nonpermissive temperature of 37 degrees C. In the classical biotype strain O395, the crp mutation increased the production of both CT and toxin-coregulated pilus (TCP) in vitro under a variety of growth conditions not normally permissive for their expression. The most dramatic increase in CT and TCP was observed with the crp mutant in Luria-Bertani (LB) medium pH 8.5, at 30 degrees C. El Tor biotype strains differ from classical strains in that they do not produce CT or TCP when grown in LB media. Incorporation of the crp mutation into El Tor strain C6706 permitted production of these proteins in LB medium pH 6.5, at 30 degrees C. In the infant mouse cholera model, the crp mutation decreased colonization in both biotypes at least 100-fold relative to the wild-type strains. The data presented here suggest a model whereby cAMP-CRP negatively regulates the expression of CT and TCP in both classical and El Tor biotypes under certain environmental conditions and also influences pathogenesis by regulating other processes necessary for optimal growth in vivo.