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Genetics of the resistance to and production of hydrogen peroxide in Streptococcus pneumoniae.

机译:肺炎链球菌对过氧化氢的抗性和产生的遗传学。

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摘要

Scope and Method of Study. Streptococcus pneumoniae (Pneumococcus) is a causative agent of severe diseases affecting young as well as older people. Pneumococcus produces very high levels of hydrogen peroxide (H2O2) (>1 mM). In the presence of pneumolysin, H2O2 has been shown to cause pneumococcal meningitis in humans. H2O2 is a by-product of oxidation of pyruvate by the pyruvate oxidase, SpxB, during the generation of acetyl PO4 in pneumococcus. Acetyl PO4 then is utilized to make ATP. Current work focuses on manipulating the genome to study the role of H2O 2 in pneumococcal pathogenesis. Previously, pneumococcal cells pregrown in the presence of lactose were shown to have an increased resistance (10-fold) to H2O2 challenge.;Findings and Conclusions. Random mutagenesis showed that the genes pyrB, truB, spr1639, and spr1813 are responsible for the resistance. Based on the DNA sequence data, it has been speculated that the spxB operon is mono-cistronic and expressed constitutively. Our experimental evidence, however, showed that maximal production of H2O2 is linked to the onset of stationary phase under static growth conditions or exposure to molecular oxygen while the transcriptional activity of spxB was constitutive even during the exponential phase of growth. Also, insertion of a reporter gene immediately down stream of the spxB gene resulted in normal H2O2 production implying that glyoxalase, a co-transcript of spxB, is not required for H2O2 production and other factors besides SpxB are needed for H2O2 production in this pathogen. We speculate that the generation of this toxin is linked to either quorum-sensing and/or availability of nutrient resources. Together, the findings helped to expand the pathogenesis pathway of H 2O2 in S. pneumoniae.
机译:研究范围和方法。肺炎链球菌(肺炎球菌)是影响年轻人和老年人的严重疾病的致病因子。肺炎球菌产生很高水平的过氧化氢(H2O2)(> 1 mM)。在存在肺炎球菌溶血素的情况下,H2O2已被证明可引起人类肺炎球菌性脑膜炎。 H2O2是在肺炎球菌中生成乙酰基PO4期间丙酮酸氧化酶SpxB氧化丙酮酸的副产物。然后利用乙酰基PO4制备ATP。当前的工作集中在操纵基因组以研究H2O 2在肺炎球菌发病机理中的作用。以前,在乳糖存在下预先生长的肺炎球菌细胞显示出对H2O2攻击的抵抗力增加(10倍)。随机诱变表明pyrB,truB,spr1639和spr1813基因是引起耐药的原因。根据DNA序列数据,已推测spxB操纵子是单顺反子且组成性表达。然而,我们的实验证据表明,在静态生长条件下或暴露于分子氧条件下,H2O2的最大产生与固定相的开始有关,而即使在指数增长期,spxB的转录活性也是组成性的。同样,在spxB基因下游立即插入一个报告基因会导致正常的H2O2产生,这意味着H2O2的产生不需要spxB的共转录物乙二醛酶,而在此病原体中H2O2的产生还需要SpxB以外的其他因素。我们推测这种毒素的产生与群体感应和/或营养资源的可用性有关。在一起,这些发现有助于扩大肺炎链球菌中H 2O2的发病机理。

著录项

  • 作者

    Tiong, Hung King.;

  • 作者单位

    Oklahoma State University.;

  • 授予单位 Oklahoma State University.;
  • 学科 Biology Genetics.
  • 学位 M.S.
  • 年度 2009
  • 页码 102 p.
  • 总页数 102
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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