Cell separation in Neisseria gonorrhoeae

淋病奈瑟菌的细胞分离

• 批准号: 8279023
• 负责人: Joseph P Dillard
• 金额: $ 18.81万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-02-05 至 2014-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8279023
• 关键词: Affect; Amidohydrolases; Animal Model; Antibiotic Resistance; Antibiotic Therapy; Antibiotics; Antibodies; Autolysis; Bacillus subtilis; Bacteria; Biochemical; Biochemical Reaction; Biological Assay; Cell Fraction; Cell Separation; Cell Wall; Cells; Cervical; Characteristics; Combined Modality Therapy; Complex; DNA; Data; Defect; Detergents; Disease; Ectopic Pregnancy; Electron Microscopy; Enzyme Inhibitor Drugs; Enzyme Inhibitors; Enzyme Interaction; Enzymes; Escherichia coli; Future; Gene Deletion; Genes; Gonorrhea; Growth; Human; Immunoprecipitation; In Vitro; Infection; Infertility; Inflammatory Response; Invaded; Knowledge; Location; Lytic; Measures; Membrane; Metabolism; Methods; Microtomy; Multi-Drug Resistance; Mutation; Neisseria gonorrhoeae; Normal Cell; Pelvic Inflammatory Disease; Peptidoglycan; Population; Process; Proteins; Role; Scaffolding Protein; Scheme; Sexually Transmitted Diseases; Shapes; System; Testing; Time; Western Blotting; Woman; amidase; antimicrobial; base; combat; drug sensitivity; in vitro Assay; inhibitor/antagonist; link protein; men; mutant; novel; pathogen; prevent; research study; resistant strain

DESCRIPTION (provided by applicant): Neisseria gonorrhoeae causes a very common sexually transmitted disease in men and women that often results in severe consequences for women including pelvic inflammatory disease, ectopic pregnancy, and infertility. The gonococcal population is becoming increasingly antibiotic resistant, and multidrug resistant strains have arisen. This proposal seeks to understand the mechanisms of peptidoglycan breakdown involved in cell separation and to develop cell separation as a target for antimicrobial therapy. Preliminary data indicate that defects in cell separation make N. gonorrhoeae more sensitive to antibiotics as well as defective in infection of human cells. Previously we demonstrated that mutations in genes for peptidoglycan degradation - amiC or ltgC - in N. gonorrhoeae cause aberrant growth, loss of cell separation, and increased autolysis. These mutants grow in large aggregates sharing a single interconnected cell wall and with a single outer membrane surrounding the aggregate. Here we will 1) determine the biochemical functions of two peptidoglycan-degrading enzymes, AmiC and LtgC, required for cell separation and develop assays that could be used to identify inhibitors of these enzymes, 2) examine the localization and possible interactions of AmiC and LtgC in gonococcal cells in order to determine the function of these enzymes for cell separation and develop assays for these enzymes in cells, and 3) determine the extent of defects of cell separation mutants for infection of human cells and for resistance to antibiotics. Knowledge gained in this study and assays developed here will facilitate the identification of antibiotics for the treatment of gonococcal diseases and for combating other bacteria that have similar mechanisms of cell separation. PUBLIC HEALTH RELEVANCE: This project will characterize the mechanisms of cell separation in the bacterial species Neisseria gonorrhoeae. These studies will develop methods to identify new antibiotics for treating gonorrhea and related diseases.

描述（由申请人提供）：淋病奈瑟氏菌在男性和女性中引起非常普遍的性传播疾病，这通常会对包括骨盆炎性疾病，异位妊娠和不孕症在内的女性造成严重后果。淋球菌种群越来越多地抗生素，并且产生了多药抗性菌株。该提案旨在理解与细胞分离有关的肽聚糖分解的机制，并发展细胞分离作为抗菌治疗的靶标。初步数据表明，细胞分离的缺陷使淋病链球菌对抗生素和人类细胞感染有缺陷更敏感。以前，我们证明了肽聚糖降解基因的突变 - 淋病中的友善或LTGC-会导致异常生长，细胞分离丧失和自溶增加。这些突变体在共享一个互连细胞壁的大骨料中生长，并与骨料周围的单个外膜一起生长。在这里我们将1）确定两种肽聚糖降解酶的生物化学功能，AMIC和LTGC，是细胞分离所需的，可用于鉴定这些酶的抑制剂所需的测定，2）检查这些酶的局部化和可能在这些分离的细胞中，以确定这些分离的细胞和LTGC的相互作用。细胞，3）确定细胞分离突变体的缺陷程度，以感染人类细胞和抗生素的耐药性。在这项研究中获得的知识和这里开发的测定将有助于鉴定抗生素治疗淋球菌疾病，并打击其他具有相似细胞分离机制的细菌。 公共卫生相关性：该项目将表征细菌种类淋病奈瑟氏菌的细胞分离机制。这些研究将开发用于鉴定用于治疗淋病和相关疾病的新抗生素的方法。