Biological activity of cytolysins produced by Gram-positive bacteria and their involvement in the response of infected

革兰氏阳性菌产生的溶细胞素的生物活性及其与感染反应的关系

基本信息

  • 批准号:
    12470063
  • 负责人:
  • 金额:
    $ 8.7万
  • 依托单位:
  • 依托单位国家:
    日本
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
  • 财政年份:
    2000
  • 资助国家:
    日本
  • 起止时间:
    2000 至 2001
  • 项目状态:
    已结题

项目摘要

Various species of Gram-positive bacteria produce cholesterol-dependent cytolysins(CDCs). We have constructed several. CDC proteins including amino- acid replacement and truncation, in-order to analyze the molecular mechanism of cytolysis and cytokine induction. CDC family proteins LLO, LSO and PLY produced by L. monocytogenes, L. seeligeri, and S. pneumoniae, respectively showed domain 4-deperident cytolytic activity and cytokine-inducing activity that was not dependent on domain 4 as well. It was found that the different domains of the same protein molecule are responsible for different biological activities. LLO induced IL-12 and IL-18 production from macrophages, and in turn these cytokines induced NK-cell dependent IFN-g. TLR2/TLR4/CD14 appeared to be involved in the cytokine response of macrophages, and domain 1-3 was capable of inducing NF-kB activation. Though most of the recombinant CDC proteins exhibited the cytokine-inducing ability, ILO derived from L. ivanovii was not active in cytokine induction despite of the high homology to LLO and LSO. It appeared that N-terminal sequence of domain 1 was highly essential for the cytokine-inducing activity, we have constructed various amino acid replacement. It was found that the PEST sequence is important in the activity. This study clearly indicated that many CDC family proteins of Gram-positive bacteria are active in cytokine-induction that is different from a well-known cytolytic activity. This novel activity appeared to be involved in the host response in the infection by CDC-producing Gram-positive bacteria.
各种革兰氏阳性细菌都会产生胆固醇依赖性细胞溶解素(CDC)。我们建造了几个。CDC蛋白质包括氨基酸替换和截短,以便分析细胞溶解和细胞因子诱导的分子机制。由L.单核细胞增多症L. seeligeri和S. pneumoniae分别显示结构域4依赖的细胞溶解活性和不依赖于结构域4的精氨酸诱导活性。发现同一蛋白质分子的不同结构域负责不同的生物活性。LLO诱导巨噬细胞产生IL-12和IL-18,反过来这些细胞因子诱导NK细胞依赖性IFN-g。TLR 2/TLR 4/CD 14参与巨噬细胞的细胞因子应答,而结构域1-3能够诱导NF-κ B活化。虽然大多数重组CDC蛋白都表现出了对精氨酸的诱导作用,但来自L. ivanovii在细胞因子诱导中没有活性,尽管与LLO和LSO具有高度同源性。结构域1的N-端序列对该蛋白的精氨酸诱导活性非常重要,我们构建了多种氨基酸替换。发现PEST序列在活性中是重要的。这项研究清楚地表明,革兰氏阳性细菌的许多CDC家族蛋白在与众所周知的细胞溶解活性不同的烟碱诱导中具有活性。这种新的活性似乎参与了产生CDC的革兰氏阳性菌感染的宿主反应。

项目成果

期刊论文数量(116)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
光山 正雄: "免疫2000-01"中山書店. 279 (2000)
光山正夫:“免疫2000-01”中山书店279(2000)。
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    0
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Baba, Hisashi et al: "Induction of gamma interferon and nitric oxide by truncated pneumolysin that lacks pore-forming activity"Infection and Immunity. 70(1). 107-113 (2002)
Baba、Hisashi 等人:“缺乏成孔活性的截短肺炎球菌溶血素诱导 γ 干扰素和一氧化氮”感染和免疫。
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    0
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Mitsuyama, Masao: "Protective immunity against intracellular-parasitic bacteria"Japanese Journal of Leprosy. 69(1), (in Japanese). 83-86 (2000)
Mitsuyama,Masao:“针对细胞内寄生细菌的保护性免疫”日本麻风病杂志。
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    0
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Mitsuyama, Masao: "Cytokine response in the host against Listeria monocytogenes intection"Igaku no Ayumi. 200, (in Japanese). (in press) (2002)
Mitsuyama,Masao:“宿主对单核细胞增多性李斯特菌感染的细胞因子反应”Igaku no Ayumi。
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    0
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光山 正雄: "細胞毒素ハンドブック"サイエンスフォーラム社. 587 (2002)
光山正雄:《细胞毒素手册》 Science Forum Inc. 587 (2002)
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    0
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MITSUYAMA Masao其他文献

Involvement of listeriolysin 0 in caspase-1 activation in macrophages infected with Listeria monocytogenes
李斯特菌溶血素 0 参与单核细胞增生李斯特菌感染的巨噬细胞中 caspase-1 的激活
  • DOI:
  • 发表时间:
    2008
  • 期刊:
  • 影响因子:
    0
  • 作者:
    HARA Hideki;TSUCHIYA Kohsuke;KAWAMURA Ikuo;NOMURA Takamasa;MITSUYAMA Masao
  • 通讯作者:
    MITSUYAMA Masao
Aspergillus fumigatusバイオフィルム形成を促進する血清中因子の同定
促进烟曲霉生物膜形成的血清因子的鉴定
  • DOI:
  • 发表时间:
    2011
  • 期刊:
  • 影响因子:
    0
  • 作者:
    HARA Hideki;TSUCHIYA Kohsuke;KAWAMURA Ikuo;NOMURA Takamasa;MITSUYAMA Masao;豊留孝仁;原英樹;豊留孝仁
  • 通讯作者:
    豊留孝仁
Involvement of listeriolysin O on caspase-1 activation in Listeria monocytogenes infection
李斯特菌溶血素 O 在单核细胞增生李斯特菌感染中参与 caspase-1 激活
  • DOI:
  • 发表时间:
    2008
  • 期刊:
  • 影响因子:
    0
  • 作者:
    HARA Hideki;TSUCHIYA Kohsuke;KAWAMURA Ikuo;NOMURA Takamasa;MITSUYAMA Masao;豊留孝仁;原英樹
  • 通讯作者:
    原英樹

MITSUYAMA Masao的其他文献

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{{ truncateString('MITSUYAMA Masao', 18)}}的其他基金

Critical role of multidrug efflux pump in the pathogenicity of Listeria monocytogenes
多药外排泵在单核细胞增生李斯特菌致病性中的关键作用
  • 批准号:
    24659196
  • 财政年份:
    2012
  • 资助金额:
    $ 8.7万
  • 项目类别:
    Grant-in-Aid for Challenging Exploratory Research
Mechanism of Listeria virulence factor-mediated regulation of innate immune response via swapping of virulence genes among Listeria species
李斯特菌毒力因子介导的通过李斯特菌种间毒力基因交换调节先天免疫反应的机制
  • 批准号:
    22390082
  • 财政年份:
    2010
  • 资助金额:
    $ 8.7万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Mechanism for intracellular action of bacterial modulin from intracellular parasitic bacteria and application
胞内寄生菌细菌调节蛋白的胞内作用机制及应用
  • 批准号:
    18390134
  • 财政年份:
    2006
  • 资助金额:
    $ 8.7万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Molecular mechanism of biological activity expressed by hemolysins derived from Listeriae inside macrophages.
巨噬细胞内李斯特菌溶血素表达的生物活性的分子机制。
  • 批准号:
    14370092
  • 财政年份:
    2002
  • 资助金额:
    $ 8.7万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Molecular mechanism of macrophage activation and intracellular parasitism by intracellular parasitic bacteria
细胞内寄生菌巨噬细胞活化及细胞内寄生的分子机制
  • 批准号:
    13226042
  • 财政年份:
    2001
  • 资助金额:
    $ 8.7万
  • 项目类别:
    Grant-in-Aid for Scientific Research on Priority Areas
Identification and functional analysis of non-antigenic factors of intracellular bacteria essential for the induction of cell-mediated protective immunity
细胞内细菌非抗原因子的鉴定和功能分析对于诱导细胞介导的保护性免疫至关重要
  • 批准号:
    09470075
  • 财政年份:
    1997
  • 资助金额:
    $ 8.7万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Basic Research on the escape mechanism of intracellular parasites and the host response in infection
细胞内寄生虫逃逸机制及宿主感染反应的基础研究
  • 批准号:
    07307004
  • 财政年份:
    1995
  • 资助金额:
    $ 8.7万
  • 项目类别:
    Grant-in-Aid for Scientific Research (A)
Escape mechanisms of intracellular bacteria and the analysis of protective immunity and tissue damage in the infected host
胞内细菌的逃逸机制及感染宿主的保护性免疫和组织损伤分析
  • 批准号:
    05454190
  • 财政年份:
    1993
  • 资助金额:
    $ 8.7万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (B)
Analysis of a common mechanism for the induction of cell-mediated immunity by intracellular bacteria and its application to host defense against bacterial infection.
分析细胞内细菌诱导细胞介导免疫的常见机制及其在宿主防御细菌感染中的应用。
  • 批准号:
    02454176
  • 财政年份:
    1990
  • 资助金额:
    $ 8.7万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (B)
Analysis of virulence factor and the mechanisms for induction of cell-mediated immunity by intracellular bacterium, Listeria monocytogenes.
胞内细菌单核细胞增生李斯特菌的毒力因子和诱导细胞介导免疫的机制分析。
  • 批准号:
    63480152
  • 财政年份:
    1988
  • 资助金额:
    $ 8.7万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (B)

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