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：
TOMOYASU Toshifumi
金额：
$ 2.3万
依托单位：
Chiba University
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

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590055/
关键词：
Salmonella TTSS AAA+ protease chaperone Lon ClpXP DnaK Dathogenic factor

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.

与各种辅助细胞内病原体类似的沙门氏菌肠鼠伤寒沙门氏菌被证明可以通过诱导应激蛋白来应对宿主有机体巨噬细胞内部的敌对条件。应力蛋白在功能上分为两组分子伴侣和蛋白酶。我们显示分子伴侣和蛋白酶在沙门氏菌的致病性方面具有重要功能。（1）AAA+ Protease Familywe的III型分泌系统（TTSS）的调节机制表明，热休克蛋白酶CLPXP和LON与S.Enterica servar servar typhimurium in Balb/c Mice中的S.enterica servar typhimurium ss.enterica Incection基本上涉及。巨噬细胞内的S. enterica血清鼠伤寒的生存和生长是必需的。我们报道了ClpXP和LON控制两个TTSS在S. enterica serovar鼠伤寒中的表达，其中一个由鞭毛调节编码，另一种是由沙门氏菌致病岛1（SPI1）（SPI1）。在巨噬细胞中完全扩散。该突变体既不能入侵培养的上皮细胞，也不能分泌SPI1中编码的任何侵袭蛋白。 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.在挑战后5天后，完全从脾，肠系膜淋巴结，Peyer的斑块，Peyer的斑块，甚至塞库姆完全清除了受到挑战的有毒和免疫的无毒沙门氏菌。我们的数据表明，与ATP依赖性蛋白酶CLPXP或LON的破坏的沙门氏菌可能对开发活疫苗菌株有用。

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）

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：
Cell Microbiol 7
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.

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：

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：
J.Bacteriol. 185(21)
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.

Lon, a stress-induced ATP-dependent protease is critically important for the systemic Salmonella infection of mice.

Lon 是一种应激诱导的 ATP 依赖性蛋白酶，对于小鼠的全身沙门氏菌感染至关重要。

DOI：
发表时间：
2003
期刊：
Infect.Immun. 71
影响因子：
0
作者：
Takaya A;Suzuki M;Matsui H;Tomoyasu T;Sashinami H;Nakane A;Yamamoto T.
通讯作者：
Yamamoto T.

Oral immunization with ATP-dependeht protease-deficient mutants protects mice against subsequent oral challenge with virulent Salmonella enterica serovar Typhimurium.

使用 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强毒肠沙门氏菌鼠伤寒血清型的口服攻击。

DOI：
发表时间：
2003
期刊：
Infect.Immun. 71(1)
影响因子：
0
作者：
Matsui H;Suzuki M;Isshiki Y;Eguchi M;Kikuchi Y;Motokawa K;Takaya A;Tomoyasu T;Yamamoto T.
通讯作者：
Yamamoto T.