ANALYSIS OF HOST-PATHOGEN INTERACTIONS IN C ELEGANS

线虫宿主-病原体相互作用的分析

• 批准号: 7955920
• 负责人: Creg Darby
• 金额: $ 3.3万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-01 至 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7955920
• 关键词: 4-glucopyranosylmannose; Anabolism; Bacteria; Bacterial Genes; Biological Models; Biology; Caenorhabditis elegans; Classification; Computer Retrieval of Information on Scientific Projects Database; Development; Fleas; Fractionation; Funding; Gastrointestinal tract structure; Genes; Glycoconjugates; Grant; Human Bites; Insecta; Institution; Invertebrates; Life; Mammals; Mass Spectrum Analysis; Medicine; Methods; Microbial Biofilms; Modeling; Pasteurella pseudotuberculosis; Pathway interactions; Plague; Polysaccharides; Research; Research Personnel; Resources; Source; Structure; United States National Institutes of Health; Yersinia; Yersinia pestis; feeding; mutant; pathogen; pathogenic bacteria; research study

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This project aims to investigate glycoconjugate structures of Yersinia pestis and Yersinia pseudotuberculosis biofilms. Biofilms are formed by most pathogenic bacteria. However, no model existed where a living host served as the biofilm target until recently. A biofilm model system is under development where Caenorhabditis elegans is infected with the above bacteria. Mutants in biofilm formation have been generated in Y. pseudotuberculosis and experiments are ongoing to generate biofilm mutants in Yersinia pestis. In bubonic plague the Y. pestis block the flea digestive tract, stimulating the insects to bite humans or other mammals repeatedly in attempts to feed. We have found that Y. pestis also blocks C. elegans from feeding. The blockage is caused by a biofilm, a polysaccharide-rich matrix synthesized by Y. pestis, and requires the bacterial genes hmsHFRS. Significantly, these genes are also required for plague bacteria to block fleas, indicating that Y. pestis uses some of the same pathways to disrupt feeding of both invertebrates. In principle, the study of the biofilm structure in wild-type and mutants will reveal structural detail and aid in the identification of the genes responsible for biofilm polysaccharide biosynthesis and its control. Preliminary study of biofilms from both Yersinia species are under way. GC-MS analysis has revealed the presence of Fuc, Xyl, Man, Glc and trace amounts of Sia, and GlcNAc. Results from MALDI-TOF MS analyses suggest the presence of homopolymers of Hex and heteropolymers containing Hex, HexNAc, deoxyHex and Pent. We are currently developing methods for systematic fractionation and analysis of the biofilm components.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 该项目旨在研究耶尔森氏菌和耶尔森氏菌生物膜生物膜的糖缀合物结构。生物膜是由大多数致病细菌形成的。 但是，直到最近才成为生物膜靶标的生物膜靶标的模型。生物膜模型系统正在开发中，秀丽隐杆线虫感染了上述细菌。 生物膜形成中的突变体已经在Y. pseudotuberculosis中产生，并且正在进行实验以在耶尔森氏菌中产生生物膜突变体。 在Bubone鼠疫中，Pestis阻止了跳蚤消化道，刺激昆虫咬人的人或其他哺乳动物，反复尝试喂食。我们发现Y. Pestis还阻止了秀丽隐杆线虫的进食。阻塞是由生物膜（由Y. Pestis合成的多糖基质）引起的，需要细菌基因HMSHFR。值得注意的是，瘟疫细菌还需要这些基因阻止跳蚤，这表明佩斯蒂斯使用一些相同的途径来破坏两种无脊椎动物的喂养。原则上，野生型和突变体中生物膜结构的研究将揭示结构细节，并有助于鉴定负责生物膜多糖生物合成及其控制的基因。来自两种Yersinia物种的生物膜的初步研究正在进行中。 GC-MS分析揭示了FUC，Xyl，Man，Glc和痕量的SIA和GLCNAC的存在。 MALDI-TOF MS分析的结果表明，存在含有六角形，六NAC，Deoxyhex和Pent的近聚物的均聚物。 我们目前正在开发用于系统分馏和分析生物膜成分的方法。