EXPRESSION AND PHASE VARIATION OF GONOCOCCAL OPA GENES

淋球菌 OPA 基因的表达和相变

• 批准号: 3746601
• 负责人: R J BELLAND
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3746601
• 关键词: Neisseria gonorrhoeae; bacterial DNA; bacterial genetics; bacterial proteins; cell adhesion; epithelium; gene expression; gene mutation; genetic regulation; genetic strain; host organism interaction; mucopolysaccharides; neutrophil; urine

Neisseria gonorrhoeae, the causative agent of gonorrhoea, expresses one or more members of the opa multigene family during the course of disease. We have studied the expression mechanisms and the biological properties of the expressed outer-membrane proteins to more clearly understand the role of this protein family in the pathogenesis of gonorrheal disease. Phase variation (on/off expression changes) occurs through a translational frameshifting mechanism dependent on "non-homologous" recombination in a series of direct, tandem repeats within each opa gene. This mechanism has been used as a paradigm for a number of other neisserial genes which phase vary using similar repetitive stretches of DNA. We have determined a number of cellular functions, primarily DNA replication and repair enzymes, which significantly influence the rates at which opa genes (and others using similar mechanisms) phase vary. Attempts to mutate these genes in N. gonorrhoeae are underway with the primary goal of creating bacterial strains which can no longer regulate phase variation of these genes at normal levels. Expression of outer-membrane Opa proteins influence the adhesive properties of N. gonorrhoeae towards epithelial cells and PMNs. We have studied the nature of the adherence and have shown that certain Opa proteins bind a family of compounds termed glycosaminoglycans, found on the surface of numerous cell types and in the external mucosal environment. We have also shown that the expression of Opa proteins may protect Opa+ bacteria from the bactericidal components of human serum in the presence of human urine. This effect is similar to that seen with added heparin and studies are underway to further characterize the nature of the protective components in human urine.

淋病的病原体淋病奈瑟菌表达一种 在疾病过程中，有一个或多个opa多基因家族的成员。 我们研究了表达机制和生物学特性 表达的外膜蛋白，以更清楚地了解 该蛋白家族在淋病发病机制中的作用。 相位变化（开/关表达变化）通过 依赖于“非同源”的平移移码机制 每个 opa 基因内一系列直接串联重复的重组。 该机制已被用作许多其他机制的范例 奈瑟氏球菌基因使用相似的重复序列进行相位变化 脱氧核糖核酸。 我们已经确定了许多细胞功能，主要是 DNA 复制和修复酶，显着影响速率 opa 基因（和其他使用类似机制的基因）相位发生变化。 正在尝试突变淋病奈瑟菌中的这些基因 主要目标是创造不再能够调节的细菌菌株 这些基因在正常水平下的相位变化。 外膜 Opa 蛋白的表达影响粘合剂 淋病奈瑟菌对上皮细胞和中性粒细胞的特性。 我们有 研究了依从性的本质并表明某些 Opa 蛋白质结合一系列称为糖胺聚糖的化合物，发现于 许多细胞类型的表面和外部粘膜 环境。 我们还表明 Opa 蛋白的表达可能 保护 Opa+ 细菌免受人血清杀菌成分的侵害 人类尿液的存在。 此效果类似于 添加了肝素，并且正在进行研究以进一步表征其性质 人体尿液中的保护成分。