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首页> 外文学位 >Identification and characterization of genes involved in survival and replication of Yersinia pestis and Yersinia pseudotuberculosis in macrophages.
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Identification and characterization of genes involved in survival and replication of Yersinia pestis and Yersinia pseudotuberculosis in macrophages.

机译：鉴定和鉴定涉及鼠疫耶尔森氏菌和假结核耶尔森氏菌在巨噬细胞中存活和复制的基因。

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摘要

Yersinia pestis and Yersinia pseudotuberculosis are closely related gram-negative bacteria that cause vastly different human diseases. Even though they use distinct routes of entry during infection, both pathogens share a common tropism for lymphoid tissue. Previous studies suggested that Y. pestis and Y. pseudotuberculosis are internalized by macrophages at early times during the infection process, but the bacteria are not degraded. In vitro experiments using cultured macrophages provided evidence that both pathogens are able to survive and replicate in macrophages. In addition, the phoP gene was shown to be required for survival of Y. pestis in macrophages and for virulence in mice. phoP encodes the response regulator of the PhoP/PhoQ two-component system, which in Salmonella is activated under low magnesium conditions and in macrophages.; I constructed Y. pestis and Y. pseudotuberculosis phoP mutants and tested them for their ability to grow in low magnesium medium and in macrophages. The Y. pseudotuberculosis phoP mutant was also tested for virulence in mice. In addition, experiments were performed to better characterize the intracellular compartment in which Y. pestis resides within the macrophage. To identify genes that were regulated by PhoP, a Tn5-lacZ screen was performed in Y. pestis.; My results show that phoP is important for proliferation of Y. pseudotuberclosis in macrophages and virulence in mice. PhoP is essential for survival of Y. pestis in macrophages due to the lack of O-antigen in this bacterium. Data presented here suggest that Y. pestis resides in a phagosome that takes on many characteristics of a phagolysosome. PhoP-regulated genes important for survival in this compartment fall into two groups: genes needed for survival under low magnesium conditions and genes required for modification of the outer membrane.; We have demonstrated that PhoP is an important virulence factor in Y. pseudotuberculosis and is required for proliferation of Y. pestis and Y. pseudotuberculosis in macrophage and in low magnesium medium. To survive in the presumably low magnesium environment of the phagosome, PhoP-regulated genes are induced within the macrophage to allow Y. pestis and Y. pseudotuberculosis to adapt to this new environment by modifying its outer membrane and expressing high affinity magnesium transporters.
机译：鼠疫耶尔森氏菌和假结核耶尔森氏菌是密切相关的革兰氏阴性细菌，可引起多种人类疾病。即使它们在感染期间使用不同的进入途径，两种病原体对于淋巴组织也具有共同的向性。先前的研究表明，在感染过程的早期，鼠疫耶尔森氏菌和假结核耶尔森氏菌被巨噬细胞内在化，但细菌并未降解。使用培养的巨噬细胞的体外实验提供了两种病原体都能够在巨噬细胞中生存和复制的证据。此外，phoP基因被证明是鼠疫耶尔森氏菌在巨噬细胞中存活和小鼠毒性的必需条件。 phoP编码PhoP / PhoQ两组分系统的响应调节剂，沙门氏菌在低镁条件下和巨噬细胞中被激活。我构建了鼠疫耶尔森氏菌和假结核耶尔森氏菌phoP突变体，并测试了它们在低镁培养基和巨噬细胞中的生长能力。还测试了假结核耶尔森氏菌phoP突变体在小鼠中的毒力。另外，进行了实验以更好地表征鼠疫耶尔森氏菌位于巨噬细胞内的细胞内区室。为了鉴定受PhoP调节的基因，在鼠疫耶尔森氏菌中进行了Tn5-lacZ筛选。我的结果表明，phoP对于巨噬细胞中的假结核耶尔森氏菌增殖和小鼠的毒力很重要。由于该细菌缺乏O-抗原，PhoP对于鼠疫耶尔森氏菌在巨噬细胞中的生存至关重要。此处提供的数据表明，鼠疫耶尔森氏菌位于具有吞噬溶酶体许多特征的吞噬体中。 PhoP调控的基因对于在该区室中的存活至关重要，分为两类：低镁条件下存活所需的基因和修饰外膜所需的基因。我们已经证明，PhoP是假结核耶尔森氏菌的重要毒力因子，是鼠疫耶尔森氏菌和假结核耶尔森氏菌在巨噬细胞和低镁培养基中增殖所必需的。为了在吞噬体的低镁环境中生存，在巨噬细胞内诱导了受PhoP调控的基因，从而允许鼠疫耶尔森氏菌和假结核耶尔森氏菌通过修饰其外膜并表达高亲和力的镁转运蛋白来适应这种新环境。

著录项

  • 作者

    Grabenstein, Jens Philip.;

  • 作者单位

    State University of New York at Stony Brook.;

  • 授予单位 State University of New York at Stony Brook.;
  • 学科 Biology Microbiology.
  • 学位 Ph.D.
  • 年度 2005
  • 页码 168 p.
  • 总页数 168
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 微生物学;
  • 关键词

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