"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.

项目总结： 阴道肺炎(Sv)是一种与早产密切相关的病原体，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 尽管它具有挑剔的性质，但直到最近才通过使用基于DNA的方法被确认为一种病原体。 由于它一直被认为是一种病原体，所以阴道沙门氏菌的生物学和发病机制仍然存在。 几乎完全没有特征。我们鉴定了一种溶血和细胞致病毒素，由S. 我们将其命名为CPTA。CPTA抗血清阻断Sv在完整人胎儿体内的穿越 提示该毒素在致病机制中起一定作用。这个项目有三个主要目标。第一 目的是评估自然定居/感染期间孕妇和胎儿对CPTA的抗体反应。第二 目的是确定CPTA在Sv.穿透和破坏胎膜中的作用。三是确定 通过建立Sv感染的小鼠模型，确定Sv与早产之间是否存在因果关系 在怀孕期间。这种新型致孔毒素的致病特性将在我们的 对这种新出现的病原体的了解。