"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： 迷走神经鞘炎（Sv）是一种与早产显著相关的病原体， 引起许多感染，包括淋病、骨关节炎、脑膜炎、菌血症和尿道炎。由于其 由于其挑剔的性质，直到最近才通过使用基于DNA的方法被确认为病原体。 由于其作为一种病原体的认识不足，目前对该菌的生物学特性和致病机理的研究还处于起步阶段。迷走神经残余 几乎完全没有特征。我们已经鉴定出由S. 我们称之为CptA。抗CptA抗血清阻断Sv穿过完整人胎儿的能力 这表明毒素在发病机制中起作用。该项目有三个主要目标。第一 评估自然定殖/感染期间母体和胎儿对CptA的抗体应答。第二 目的是确定CptA在Sv穿过和损伤胎膜中的作用。三是确定 通过建立小鼠Sv感染模型，研究Sv与早产之间的关系是否是因果关系 孕期这种新的成孔毒素的发病机制特征将在我们的研究中开辟新的领域。 了解这种新出现的病原体。