The function of NGO2115 in the Neisseria gonorrhoeae oxidative stress resistance
NGO2115在淋病奈瑟菌氧化应激抵抗中的作用
基本信息
- 批准号:7805086
- 负责人:
- 金额:$ 5.05万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2010
- 资助国家:美国
- 起止时间:2010-03-01 至 2012-02-29
- 项目状态:已结题
- 来源:
- 关键词:AddressBacteriaBiological AssayBiologyCell RespirationCellsCodeComplementCountryDNADetectionDiseaseEnvironmentExhibitsGene TargetingGenesGenetic TranscriptionGenitourinary systemGoalsGonorrheaHealthHumanHydrogen PeroxideImmuneImmune systemIn VitroLiteratureMissionMutateMutationNatural ImmunityNeisseria gonorrhoeaeNeisseria meningitidisOrganismOxidantsOxidative StressPathogenesisPost-Translational Protein ProcessingPredispositionProteinsPublic HealthReactive Oxygen SpeciesRegulationRegulator GenesResistanceReverse Transcriptase Polymerase Chain ReactionRoleSexually Transmitted DiseasesSurfaceTechniquesTestingTranscriptTranscriptional RegulationUnited StatesUnited States National Institutes of Healthbacterial resistancebiological adaptation to stresscommensal microbesdefense responsegene functionin vivokillingsmutantneutrophilnoveloxidationoxidative damagepathogenresearch studyresistance mechanismresponse
项目摘要
DESCRIPTION (provided by applicant): The objective of this proposal is to characterize a novel component of the Neisseria gonorrhoeae oxidative stress and innate immunity defense responses. This proposal is relevant to the mission of the NIH in that N. gonorrhoeae is responsible for a significant health burden in this country and that it addresses a fundamental aspect of N. gonorrhoeae biology that has implications in the pathogenesis of the organism. N. gonorrhoeae is an ideal candidate for studying bacterial oxidative resistance mechanisms due to its obligate association with the oxidative environment of the human host. Preliminary experiments have identified a hydrogen peroxide-induced gene, NG02115, that when mutated confers enhanced resistance of N. gonorrhoeae to hydrogen peroxide, indicating a role for this protein in the oxidative stress response. The NG02115 transcript encodes a putative transcriptional regulator that is hypothesized to control expression of target genes that function in the oxidative stress response. The major focus of Aim 1 will be to determine how NG02115 controls resistance or sensitivity to oxidants by identifying NG02115 target genes. This goal will be accomplished using quantitative RT-PCR and transcriptional microarray techniques. A second goal of Aim 1 is to investigate species-specific differences between the N. gonorrhoeae and Neisseria meningitidis NG02115 coding sequences that may have functional consequences. The overall objective of Aim 2 is to characterize the contribution of NG02115 and its target genes to the N. gonorrhoeae oxidative stress response. Strains harboring mutations in NG02115 and NG02115 regulatory targets will be tested using in vitro killing assays for sensitivity to several types of reactive oxygen species. The amount of macromolecular oxidative damage that accumulates in these strains will also be determined by quantifying oxidative DNA and protein modifications. Together, these experiments will identify the specific types of oxidative stress that NG02115 and its target genes respond to. The final objective of Aim 2 will be to determine the contribution of NG02115 and NG0215 target genes in facilitating either resistance or sensitivity to primary human neutrophils. These neutrophil susceptibility experiments will establish the contribution of NG02115 and its target genes to interactions with a physiologically relevant component of the innate immune system.
Relevance: Gonorrhea is a sexually transmitted infection that is a major contributor to the public health burden in the United States. This proposal aims to characterize a novel mechanism by which the causative agent. Neisseria gonorrhoeae survives oxidative stress and killing by innate immune cells and thus is able to promote disease within the human host.
描述(由申请人提供):本提案的目的是表征淋球菌氧化应激和先天免疫防御反应的一种新成分。这项建议与美国国立卫生研究院的使命相关,因为淋病奈瑟菌在这个国家造成了巨大的健康负担,而且它涉及淋病奈瑟菌生物学的一个基本方面,这一方面对该生物体的发病机制有影响。淋病奈瑟菌是研究细菌氧化耐药机制的理想候选者,因为它与人类宿主的氧化环境密切相关。初步实验已经确定了过氧化氢诱导的基因NG02115,当突变时,淋球菌对过氧化氢的抵抗力增强,表明这种蛋白在氧化应激反应中发挥作用。NG02115转录本编码一个假定的转录调节因子,该转录调节因子被认为控制在氧化应激反应中起作用的靶基因的表达。目标1的主要焦点将是通过识别NG02115目标基因来确定NG02115如何控制对氧化剂的抗性或敏感性。这一目标将使用定量RT-PCR和转录微阵列技术来实现。目标1的第二个目标是研究淋球菌和脑膜炎奈瑟氏菌NG02115编码序列之间的物种特异性差异,这些序列可能具有功能后果。目标2的总体目标是确定NG02115及其靶基因对淋病奈瑟菌氧化应激反应的贡献。在NG02115和NG02115调控靶点发生突变的菌株将使用体外杀伤试验进行测试,以确定其对几种类型的活性氧物种的敏感性。在这些菌株中积累的大分子氧化损伤的量也将通过量化氧化DNA和蛋白质修饰来确定。总之,这些实验将确定NG02115及其目标基因响应的特定类型的氧化应激。目标2的最终目标将是确定NG02115和NG0215目标基因在促进对原始人类中性粒细胞的抵抗或敏感性方面的贡献。这些中性粒细胞敏感性实验将确定NG02115及其目标基因对与先天免疫系统的生理相关成分相互作用的贡献。
相关性:淋病是一种性传播感染,是美国公共卫生负担的主要贡献者。这项提议旨在描述一种新的机制,通过这种机制,致病因子。淋球菌在氧化应激和先天免疫细胞的杀伤下存活下来,因此能够在人类宿主内促进疾病。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
MARK T. ANDERSON其他文献
MARK T. ANDERSON的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('MARK T. ANDERSON', 18)}}的其他基金
Genetic variation of the Serratia marcescens capsule polysaccharide locus and its contribution to bloodstream infection
粘质沙雷氏菌荚膜多糖位点的遗传变异及其对血流感染的影响
- 批准号:
10116278 - 财政年份:2020
- 资助金额:
$ 5.05万 - 项目类别:
The function of NGO2115 in the Neisseria gonorrhoeae oxidative stress resistance
NGO2115在淋病奈瑟菌氧化应激抵抗中的作用
- 批准号:
8039183 - 财政年份:2010
- 资助金额:
$ 5.05万 - 项目类别:
相似国自然基金
Segmented Filamentous Bacteria激活宿主免疫系统抑制其拮抗菌 Enterobacteriaceae维持菌群平衡及其机制研究
- 批准号:81971557
- 批准年份:2019
- 资助金额:65.0 万元
- 项目类别:面上项目
电缆细菌(Cable bacteria)对水体沉积物有机污染的响应与调控机制
- 批准号:51678163
- 批准年份:2016
- 资助金额:64.0 万元
- 项目类别:面上项目
相似海外基金
Cell Wall Formation in Rod Shaped Bacteria
杆状细菌细胞壁的形成
- 批准号:
BB/Y003187/1 - 财政年份:2024
- 资助金额:
$ 5.05万 - 项目类别:
Research Grant
Did light dictate ancient diversification of phylogeny and cell structure in the domain bacteria?
光是否决定了细菌领域的古代系统发育和细胞结构的多样化?
- 批准号:
24H00582 - 财政年份:2024
- 资助金额:
$ 5.05万 - 项目类别:
Grant-in-Aid for Scientific Research (A)
Conference: Symposium on the Immune System of Bacteria
会议:细菌免疫系统研讨会
- 批准号:
2349218 - 财政年份:2024
- 资助金额:
$ 5.05万 - 项目类别:
Standard Grant
DNA replication dynamics in living bacteria
活细菌中的 DNA 复制动态
- 批准号:
23K25843 - 财政年份:2024
- 资助金额:
$ 5.05万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
DYNBIOTICS - Understanding the dynamics of antibiotics transport in individual bacteria
DYNBIOTICS - 了解抗生素在单个细菌中转运的动态
- 批准号:
EP/Y023528/1 - 财政年份:2024
- 资助金额:
$ 5.05万 - 项目类别:
Research Grant
NPBactID - Differential binding of peptoid functionalized nanoparticles to bacteria for identifying specific strains
NPBactID - 类肽功能化纳米粒子与细菌的差异结合,用于识别特定菌株
- 批准号:
EP/Y029542/1 - 财政年份:2024
- 资助金额:
$ 5.05万 - 项目类别:
Fellowship
Assembly of the matrix that supports bacteria living in biofilms
支持生活在生物膜中的细菌的基质的组装
- 批准号:
2468773 - 财政年份:2024
- 资助金额:
$ 5.05万 - 项目类别:
Studentship
BacNLR - Functional diversity of NLRs in multicellular bacteria
BacNLR - 多细胞细菌中 NLR 的功能多样性
- 批准号:
EP/Z000092/1 - 财政年份:2024
- 资助金额:
$ 5.05万 - 项目类别:
Research Grant
Manipulating two-component systems to activate cryptic antibiotic pathways in filamentous actinomycete bacteria
操纵双组分系统激活丝状放线菌中的神秘抗生素途径
- 批准号:
BB/Y005724/1 - 财政年份:2024
- 资助金额:
$ 5.05万 - 项目类别:
Research Grant