Peptidoglycan metabolism and fragment release

肽聚糖代谢和片段释放

基本信息

批准号：
8463110
负责人：
Joseph P Dillard
金额：
$ 52万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-05-01 至 2017-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8463110
关键词：
Affect Alanine Amidohydrolases Antibodies Bacteria Bacterial Infections Biochemical Bordetella pertussis Carboxypeptidase Cause of Death Cell Separation Cell Wall Cell physiology Cells Cleaved cell Data Detection Disease Endopeptidases Enzyme Gene Enzymes Epithelial Gene Mutation Genes Genetic Transcription Gonorrhea Growth Human Immune response Infection Inflammatory Response Knock-out Knockout Mice Location Lytic Mammalian Oviducts Metabolism Modeling Molecular Mutate Mutation Neisseria gonorrhoeae Organ Culture Techniques Pathway interactions Pelvic Inflammatory Disease Peptide Hydrolases Peptides Peptidoglycan Play Process Production RNA Sequences Reaction Recycling Role Shigella flexneri Side Signal Transduction Squid System Testing Tissues Vibrio fischeri Virulence Factors Woman amidase biological systems cell injury cell type crosslink genetic manipulation migration mutant neutrophil pathogen peptidoglycan monomer receptor response

项目摘要

DESCRIPTION (provided by applicant): Bacterial growth and division requires constant degradation and reassembly of the peptidoglycan cell wall. This process generates small peptidoglycan fragments that can be released by the bacteria and sensed by host cells, often inducing an inflammatory response. In infections caused by Neisseria gonorrhoeae, Bordetella pertussis, or Shigella flexneri, peptidoglycan fragments are thought to induce a large inflammatory response that exacerbates disease or is largely responsible for the cell damage occurring during the disease. In the organ culture model of gonococcal pelvic inflammatory disease, these peptidoglycan fragments recapitulate the tissue damage seen in women with the disease. The mechanisms for toxic peptidoglycan fragment production and subsequent release are not known for any of the bacteria that release these fragments. Furthermore bacteria can affect the host response by processing the peptidoglycan in different ways, resulting in detection and signaling through different pathways. In N. gonorrhoeae the composition of released peptidoglycan fragments is different from that which makes up the cell wall, suggesting that the bacteria may specifically process peptidoglycan fragments from cell wall degradation to produce specific products that alter or effect host cell processes. In these studies we will identify enzymes important for the production and release of toxic peptidoglycan fragments by N. gonorrhoeae, characterize the function of these enzymes, produce mutants defective in enzyme function and thus defective in toxic fragment production, and determine the effects of different released peptidoglycan fragments in gonococcal infection of primary human neutrophils and Fallopian tube tissue.

描述（由申请人提供）：细菌生长和分裂需要持续降解和重新组装肽聚糖细胞壁。该过程产生了小的肽聚糖片段，这些片段可以由细菌释放并被宿主细胞感测，通常会引起炎症反应。在由淋病奈瑟氏菌引起的感染中，肽聚糖片段被认为会诱导大量的炎症反应，从而加剧了疾病，或者在很大程度上造成了疾病期间的细胞损伤。在淋球菌骨盆炎性疾病的器官培养模型中，这些肽聚糖碎片概括了该疾病女性中的组织损害。有毒肽聚糖片段产生和随后释放的机制尚不以任何释放这些片段的细菌而闻名。此外，细菌可以通过以不同的方式处理肽聚糖来影响宿主反应，从而通过不同的途径进行检测和信号传导。在淋病链球菌中，释放的肽聚糖片段的组成与构成细胞壁的碎片不同，这表明细菌可能会特异性地处理细胞壁降解中的肽聚糖片段，从而产生改变或影响宿主细胞过程的特定产物。在这些研究中，我们将确定对淋病猪笼草的毒性肽聚糖片段至关重要的酶，表征了这些酶的功能，在酶功能中产生突变体有缺陷，从而在毒性片段中产生缺陷，并确定不同释放的释放的效果原发性人类中性粒细胞和输卵管组织的淋球菌感染中的肽聚糖片段。