Bile acid-induced virulence gene expression of Vibrio parahaemolyticus reveals a novel therapeutic potential for bile acid sequestrants.
Bile acid-induced virulence gene expression of Vibrio parahaemolyticus reveals a novel therapeutic potential for bile acid sequestrants.
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DOI：
10.1371/journal.pone.0013365
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发表时间：
2010-10-13
期刊：
影响因子：
3.7
通讯作者：
Iida T
中科院分区：
文献类型：
--
作者：
Gotoh K;Kodama T;Hiyoshi H;Izutsu K;Park KS;Dryselius R;Akeda Y;Honda T;Iida T
副溶血性弧菌是一种引起人类胃肠炎的细菌病原体。致病岛（Vp-PAI）编码的III型分泌系统（T3 SS 2）是引起肠毒性的主要因素，Vp-PAI编码基因的表达受两个转录调控因子VtrA和VtrB的调控。然而，尚未鉴定出VP-PAI基因的宿主衍生诱导剂。在这里，我们证明了胆汁诱导生产T3 SS 2相关蛋白的渗透条件下相当于那些在肠腔。我们还表明，胆汁诱导vtrA介导的vtrB转录。胆汁反应基因的转录组分析显示，胆汁强烈诱导Vp-PAI基因的表达，在vtrA依赖的方式。胆汁酸螯合剂考来烯胺可减弱胆汁的诱导活性。最后，我们证明了考来烯胺对肠毒性的体内保护作用，并表明在感染不同类型的副溶血性弧菌或携带相同类型T3 SS的非O 1/非O 139霍乱弧菌菌株时观察到类似的保护作用。总之，这些结果提供了一个深入了解细菌如何通过Vp-PAI基因的巧妙作用，可以利用一个否则敌对的宿主环境。结果还揭示了广泛使用的胆汁酸螯合剂在肠道细菌感染中的新的治疗潜力。
Vibrio parahaemolyticus, a bacterial pathogen, causes human gastroenteritis. A type III secretion system (T3SS2) encoded in pathogenicity island (Vp-PAI) is the main contributor to enterotoxicity and expression of Vp-PAI encoded genes is regulated by two transcriptional regulators, VtrA and VtrB. However, a host-derived inducer for the Vp-PAI genes has not been identified. Here, we demonstrate that bile induces production of T3SS2-related proteins under osmotic conditions equivalent to those in the intestinal lumen. We also show that bile induces vtrA-mediated vtrB transcription. Transcriptome analysis of bile-responsive genes revealed that bile strongly induces expression of Vp-PAI genes in a vtrA-dependent manner. The inducing activity of bile was diminished by treatment with bile acid sequestrant cholestyramine. Finally, we demonstrate an in vivo protective effect of cholestyramine on enterotoxicity and show that similar protection is observed in infection with a different type of V. parahaemolyticus or with non-O1/non-O139 V. cholerae strains of vibrios carrying the same kind of T3SS. In summary, these results provide an insight into how bacteria, through the ingenious action of Vp-PAI genes, can take advantage of an otherwise hostile host environment. The results also reveal a new therapeutic potential for widely used bile acid sequestrants in enteric bacterial infections.
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DOI：
10.1073/pnas.0409559102
发表时间：
2005-02-22
影响因子：
11.1
作者：
Hung, DT;Mekalanos, JJ
通讯作者：
Mekalanos, JJ
影响因子：
3.4
作者：
Kodama, Toshio;Rokuda, Mitsuhiro;Honda, Takeshi
通讯作者：
Honda, Takeshi
影响因子：
168.9
作者：
Makino, K;Oshima, K;Iida, T
通讯作者：
Iida, T
影响因子：
3.1
作者：
Fabbri, A;Falzano, L;Fiorentini, C
通讯作者：
Fiorentini, C
DOI：
10.3181/00379727-102-25358
发表时间：
1959-01-01
影响因子：
--
作者：
BERGEN, SS;VANITALLIE, TB;SEBRELL, WH
通讯作者：
SEBRELL, WH