"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”

基本信息

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
项目类别：
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

项目摘要

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.

项目摘要： Sneathia阴道（SV）正在成为一种与早产显着相关的病原体，并且可以引起许多感染，包括羊水炎，骨关节炎，脑膜炎，菌血症和尿道炎。由于它的挑剔的性质，它直到最近才通过使用基于DNA的方法被认为是病原体。因为它被低估为病原体，所以阴道链球菌的发病机理仍然存在几乎完全没有特色。我们已经确定了S。产生的溶血和细胞致病毒素我们命名为CPTA的阴道。反对CPTA的抗血清消除了完整的人胎儿的SV遍历膜表明毒素在发病机理中起作用。该项目有三个主要目标。第一个是为了评估自然定殖/感染期间对CPTA的母体和胎儿抗体反应。第二个是确定CPTA在SV中对胎儿膜的遍历和损害的作用。第三是确定 SV与早产之间的关联是否是通过开发SV感染的小鼠模型的因果怀孕期间。这种新型孔形成毒素的发病机理表征将在我们的了解这种新兴病原体。