"Role of the cytotoxin, CptA, from the emerging bacterial pathogen Sneathia vaginalis, in pathogenesis"

“来自新兴细菌病原体阴道球菌的细胞毒素 CptA 在发病机制中的作用”

• 批准号: 10593631
• 负责人: KIMBERLY Kay JEFFERSON
• 金额: $ 23.29万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-11-04 至 2024-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10593631
• 关键词: Address; Amino Acids; Anaerobic Bacteria; Animals; Antibodies; Antibody Response; Bacteremia; Binding; Biological Models; Biology; Blood specimen; Clinical Microbiology; Culture-independent methods; Cytotoxin; DNA; Data; Degenerative polyarthritis; Detection; Development; Endometritis; Enzyme-Linked Immunosorbent Assay; Epithelial Cells; Etiology; Exhibits; Female; Fetal Death; Fetal Membranes; Genes; Goals; Healthy People 2020; Histophilus; Human; Immune; Immune response; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; In Vitro; Inbred BALB C Mice; Incidence; Infection; Invaded; Measurement; Mediating; Membrane; Meningitis; Methods; Modeling; Mothers; Mus; Names; Nature; Pathogenesis; Peripheral; Phylogenetic Analysis; Pilot Projects; Placenta; Plasma; Play; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Premature Birth; Proteins; Recombinants; Role; Route; Rupture; Sampling; Sepsis; Serum; Specimen; Surface; Surveys; Swab; Term Birth; Testing; Time; Toxin; Umbilical Cord Blood; United States National Institutes of Health; Urethritis; Uterine cavity; Uterus; Vagina; Virulence Factors; design; emerging pathogen; fetal; human subject; in vivo; infant death; infant morbidity/mortality; microbiome research; mouse model; mutant; neonatal morbidity; neonate; novel; pathogen; pathogenic bacteria; pregnant; preterm premature rupture of membranes; receptor; reproductive tract; trophoblast; vaginal microbiota

PROJECT SUMMARY: Sneathia vaginalis (Sv) is emerging as a pathogen that is significantly associated with preterm birth and can cause numerous infections including amnionitis, osteoarthritis, meningitis, bacteremia, and urethritis. Due to its fastidious nature, it has only recently been recognized as a pathogen through the use of DNA-based methods. Because it has been under-recognized as a pathogen, the biology and the pathogenesis of S. vaginalis remain almost entirely uncharacterized. We have identified a hemolytic and cytopathogenic toxin produced by S. vaginalis that we have named CptA. Antiserum against CptA abrogates traversal of Sv across intact human fetal membranes suggesting that the toxin plays a role in pathogenesis. This project has three main goals. The first is to assess the maternal and fetal antibody response to CptA during natural colonization/infection. The second is to establish the role of CptA in traversal of and damage to fetal membranes by Sv. The third is to determine whether the association between Sv and preterm birth is causal by developing a mouse model of Sv infection during pregnancy. pathogenesis Characterization of this novel pore-forming toxin will break ground in our understanding of this emerging pathogen.

项目概要： 阴道奈瑟菌 (Sv) 正在成为一种与早产显着相关的病原体，并且可以 引起多种感染，包括羊膜炎、骨关节炎、脑膜炎、菌血症和尿道炎。由于其 由于其性质挑剔，最近才通过基于 DNA 的方法将其确认为病原体。 由于其作为病原体的认识不足，阴道链球菌的生物学和发病机制仍然存在 几乎完全没有特征。我们已经鉴定出由链球菌产生的溶血性和致细胞病变毒素。 我们将其命名为 CptA。 CptA 抗血清消除了 Sv 穿过完整人类胎儿的能力 膜表明毒素在发病机制中发挥作用。该项目有三个主要目标。第一个 目的是评估自然定植/感染期间母体和胎儿抗体对 CptA 的反应。第二个 目的是确定 CptA 在 Sv 穿过和损伤胎膜中的作用。第三是确定 通过建立 Sv 感染小鼠模型来确定 Sv 与早产之间是否存在因果关系 怀孕期间。这种新型成孔毒素的发病机制表征将在我们的研究中取得突破 了解这种新出现的病原体。