Attenuation of Edwardsiella tarda Virulence by Small Peptides That Interfere with LuxS/Autoinducer Type 2 Quorum Sensing

Attenuation of Edwardsiella tarda Virulence by Small Peptides That Interfere with LuxS/Autoinducer Type 2 Quorum Sensing
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通过干扰 LuxS/自诱导剂 2 型群体感应的小肽来减弱迟缓爱德华氏菌的毒力

DOI:
10.1128/aem.02690-08
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发表时间:
2009-05
影响因子:
4.4
通讯作者:
Zhang, Min
Zhang, Min
中科院分区:
生物学2区
文献类型:
--
作者:
Hu, Yong-hua;Jiao, Xu-dong;Sun, Li;Zhang, Min

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摘要迟缓爱德华氏菌是一种革兰氏阴性病原体,宿主范围广泛,包括人类、动物和鱼类。最近的研究表明,LuxS/自诱导剂 2 型 (AI-2) 群体感应系统与迟缓艾美耳球菌的毒力有关。在本研究中,发现分别缺失催化位点(C 位点)和酪氨酸激酶磷酸化位点的 E. tarda LuxS 突变体在功能上无活性,并且这些功能失调的突变体可以干扰野生型 LuxS 的活性。鉴定出两个小肽 5411 和 5906,它们与 LuxS 的 C 位点具有序列同一性。 5411 和 5906 被证明是 AI-2 活性的抑制剂,可以削弱致病性 E. tarda 菌株 TX1 的感染性。 5411 和 5906 对 AI-2 活性的抑制作用是在 LuxS 上发挥的,这些肽与 LuxS 发生特异性相互作用。 TX1 中 5411 和 5906 的表达具有多种效应(改变生物膜的产生和某些毒力相关基因的表达),这与 luxS 表达中断引起的效应相似。进一步的研究发现,5411和5906很可能从表达它们的菌株中释放出来,如果TX1在附近,则被TX1捕获。基于这一观察,以从质粒来源表达 5411 的鱼共生分离株的形式构建了组成型 5411 生产者(假单胞菌菌株 FP3/pT5411)。鱼类中 FP3/pT5411 的存在会减弱 TX1 的毒力。最后,研究表明直接从组织表达 5411 的鱼表现出增强的对 TX1 感染的抵抗力。
ABSTRACT Edwardsiella tarda is a gram-negative pathogen with a broad host range that includes humans, animals, and fish. Recent studies have shown that the LuxS/autoinducer type 2 (AI-2) quorum sensing system is involved in the virulence of E. tarda. In the present study, it was found that the E. tarda LuxS mutants bearing deletions of the catalytic site (C site) and the tyrosine kinase phosphorylation site, respectively, are functionally inactive and that these dysfunctional mutants can interfere with the activity of the wild-type LuxS. Two small peptides, 5411 and 5906, which share sequence identities with the C site of LuxS, were identified. 5411 and 5906 proved to be inhibitors of AI-2 activity and could vitiate the infectivity of the pathogenic E. tarda strain TX1. The inhibitory effect of 5411 and 5906 on AI-2 activity is exerted on LuxS, with which these peptides specifically interact. The expression of 5411 and 5906 in TX1 has multiple effects (altering biofilm production and the expression of certain virulence-associated genes), which are similar to those caused by interruption of luxS expression. Further study found that it is very likely that 5411 and 5906 can be released from the strains expressing them and, should TX1 be in the vicinity, captured by TX1. Based on this observation, a constitutive 5411 producer (Pseudomonas sp. strain FP3/pT5411) was constructed in the form of a fish commensal isolate that expresses 5411 from a plasmid source. The presence of FP3/pT5411 in fish attenuates the virulence of TX1. Finally, it was demonstrated that fish expressing 5411 directly from tissues exhibit enhanced resistance against TX1 infection.
DOI: 10.1007/s12275-008-0038-x
发表时间: 2008-07
期刊: The Journal of Microbiology
影响因子: --
作者:
F. Wang;Shuang Cheng;Kun Sun;Li Sun
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发表时间: 2001-08-01
期刊: MICROBIOLOGY-SGM
影响因子: 2.8
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通讯作者: Lidstrom, ME
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发表时间: 2005-12-01
期刊: MICROBIOLOGY-SGM
影响因子: 2.8
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Bjarnsholt, T;Jensen, PO;Givskov, M
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DOI: 10.1128/jb.188.1.305-316.2006
发表时间: 2006-01-01
影响因子: 3.2
作者:
Barrios, AFG;Zuo, RJ;Wood, TK
通讯作者: Wood, TK
DOI: --
发表时间: --
期刊: --
影响因子: --
作者:
K. Livak;Thomas D. Schmittgen
通讯作者: K. Livak;Thomas D. Schmittgen