Regulatory mechanisms of type III secretion system by molecular chaperones and proteases in Salmonella enterica serovar Typhimurium.

鼠伤寒沙门氏菌分子伴侣和蛋白酶对 III 型分泌系统的调节机制。

基本信息

  • 批准号:
    15590055
  • 负责人:
  • 金额:
    $ 2.3万
  • 依托单位:
  • 依托单位国家:
    日本
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
  • 财政年份:
    2003
  • 资助国家:
    日本
  • 起止时间:
    2003 至 2004
  • 项目状态:
    已结题

项目摘要

Salmonella enterica serovar Typhimurium, similar to various facultative intracellular pathogens, has been shown to respond to the hostile conditions inside macrophages of the host organism by inducing stress proteins. The stress proteins are functionally divided into two groups, molecular chaperones and proteases. We showed molecular chaperones and proteases have an important function for the Salmonella Pathogenicity.(1)Regulatory mechanisms of type III secretion system (TTSS) by AAA+ protease familyWe showed that the heat shock proteases ClpXP and Lon are essentially involved in systemic infection with S.enterica serovar Typhimurium in BALB/c mice. ClpXP and Lon are required for the survival and growth of S.enterica serovar Typhimurium within macrophages. We reported that ClpXP and Lon control the expression of two TTSSs in S.enterica serovar Typhimurium in which one is encoded by flagellar regulon and another is by Salmonella Pathogenicity Island 1(SPI1).(2)Regulatory mechanisms of TTSS by molecular chaperoneMacrophage survival assays revealed that the DnaK/DnaJ-depleted mutant could not survive or proliferate at all within macrophages. This mutant could neither invade cultured epithelial cells nor secrete any of the invasion proteins encoded within SPI1. We also showed that the DnaK/DnaJ-depleted mutant could not secrete flagellar proteins and SPI2 effector proteins encoded by TTSSs.(3)Development of Salmonella live vaccine.Immunization with the ClpXP-or Lon-deficient strain protected mice against oral challenge with the S. enterica serovar Typhimurium virulent strain. Both the challenged virulent and immunized avirulent salmonellae were completely cleared from the spleen, mesenteric lymph nodes, Peyer's patches, and even cecum 5 days after the challenge. Our data indicated that Salmonella with a disruption of the ATP-dependent protease ClpXP or Lon could be useful in developing a live vaccine strain.
肠沙门氏菌鼠伤寒血清型与各种兼性细胞内病原体相似,已被证明可以通过诱导应激蛋白对宿主生物体巨噬细胞内的不利条件做出反应。应激蛋白在功能上分为两组:分子伴侣和蛋白酶。我们发现分子伴侣和蛋白酶对沙门氏菌致病性具有重要作用。(1)AAA+蛋白酶家族对III型分泌系统(TTSS)的调节机制我们发现热休克蛋白酶ClpXP和Lon本质上参与了BALB/c小鼠鼠伤寒沙门氏菌的全身感染。 ClpXP 和 Lon 是鼠伤寒沙门氏菌在巨噬细胞内生存和生长所必需的。我们报道ClpXP和Lon控制鼠伤寒沙门氏菌两种TTSS的表达,其中一种由鞭毛调节子编码,另一种由沙门氏菌致病性岛1(SPI1)编码。(2)分子伴侣对TTSS的调节机制巨噬细胞存活实验表明,DnaK/DnaJ缺失的突变体不能存活或不能存活。 在巨噬细胞内完全增殖。该突变体既不能侵入培养的上皮细胞,也不能分泌 SPI1 内编码的任何侵入蛋白。我们还表明,DnaK/DnaJ 缺失的突变体不能分泌由 TTSS 编码的鞭毛蛋白和 SPI2 效应蛋白。(3)沙门氏菌活疫苗的开发。用 ClpXP 或 Lon 缺陷菌株进行免疫可以保护小鼠免受鼠伤寒沙门氏菌强毒菌株的口服攻击。攻击后5天,攻击的强毒力和免疫的无毒力沙门氏菌均从脾脏、肠系膜淋巴结、派尔氏集结甚至盲肠中完全清除。我们的数据表明,破坏 ATP 依赖性蛋白酶 ClpXP 或 Lon 的沙门氏菌可用于开发活疫苗株。

项目成果

期刊论文数量(25)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
A new heat-shock gene agsA, which encodes a small chaperone involved in suppressing protein aggregation in Salmonella entrica serovar Typhimurium.
一种新的热休克基因 agsA,编码参与抑制鼠伤寒沙门氏菌蛋白质聚集的小分子伴侣。
  • DOI:
  • 发表时间:
    2003
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Tomoyasu T;Takaya A;Sasaki T;Nagase T;Kikuno R;Morioka M;Yamamoto T.
  • 通讯作者:
    Yamamoto T.
Matsui H: "Oral immunization with ATP-dependent protease-deficient mutants protects mice against subsequent oral challenge with virulent Salmonella enterica serovar Typhimurium."Infect.Immun.. 71. 30-39 (2003)
Matsui H:“用 ATP 依赖性蛋白酶缺陷型突变体进行口服免疫可以保护小鼠免受随后的有毒鼠伤寒沙门氏菌口服攻击。”Infect.Immun.. 71. 30-39 (2003)
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
Depression of Salmonella pathogenicity island 1 genes within macrophages leads to rapid apoptosis via caspase-1- and caspase-3-dependent pathways.
巨噬细胞内沙门氏菌致病性岛 1 基因的抑制会通过 caspase-1 和 caspase-3 依赖性途径导致快速细胞凋亡。
  • DOI:
  • 发表时间:
    2005
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Takaya A;Suzuki A;Kikuchi Y;Eguchi M;Isogai E;Tomoyasu T;Yamamoto T.
  • 通讯作者:
    Yamamoto T.
Oral immunization with ATP-dependent protease-deficient mutants protects mice against subsequent oral challenge with virulent Salmonella enterica serovar Typhimurium
  • DOI:
    10.1128/iai.71.1.30-39.2003
  • 发表时间:
    2003-01-01
  • 期刊:
  • 影响因子:
    3.1
  • 作者:
    Matsui, H;Suzuki, M;Yamamoto, T
  • 通讯作者:
    Yamamoto, T
Derepression of Salmonella pathogenicity island 1 genes within macrophages leads to rapid apoptosis via caspase‐1‐ and caspase‐3‐dependent pathways
  • DOI:
    10.1111/j.1462-5822.2004.00435.x
  • 发表时间:
    2004-08
  • 期刊:
  • 影响因子:
    3.4
  • 作者:
    A. Takaya;A. Suzuki;Y. Kikuchi;M. Eguchi;E. Isogai;T. Tomoyasu;Tomoko Yamamoto
  • 通讯作者:
    A. Takaya;A. Suzuki;Y. Kikuchi;M. Eguchi;E. Isogai;T. Tomoyasu;Tomoko Yamamoto
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TOMOYASU Toshifumi其他文献

TOMOYASU Toshifumi的其他文献

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{{ truncateString('TOMOYASU Toshifumi', 18)}}的其他基金

Investigation of the regulatory mechanism for the production of a human specific cytolysin, a crucial factor for the infectivity of Streptococcus intermedius
研究人类特异性溶细胞素产生的调节机制,这是中间链球菌感染性的关键因素
  • 批准号:
    23590510
  • 财政年份:
    2011
  • 资助金额:
    $ 2.3万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Regulation of pathogenicity by the heat shock chaperone and the protease in streptococci
链球菌中热休克伴侣和蛋白酶的致病性调节
  • 批准号:
    19590449
  • 财政年份:
    2007
  • 资助金额:
    $ 2.3万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Expression control mechanisms of LEE pathogenic factors by AAA proteases in Enterohaemorrhagic and Enteropathogenic Eschericha coli
AAA蛋白酶在肠出血性和肠病性大肠杆菌中表达LEE致病因子的表达控制机制
  • 批准号:
    17590387
  • 财政年份:
    2005
  • 资助金额:
    $ 2.3万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)

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番茄黄单胞菌发病机制所需的热重复 TTSS 效应子 XopN 的表征
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肠出血性大肠杆菌对 TTSS 依赖性炎症细胞因子产生的抑制分析。
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