The Virulome of Infectious Preterm Birth (Project 2; PI: Jefferson)

传染性早产的病毒组（项目 2；负责人：Jefferson）

• 批准号: 8655803
• 负责人: KIMBERLY Kay JEFFERSON
• 金额: $ 24.64万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-05-01 至 2017-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8655803
• 关键词: Affect; African American; Amniotic Fluid; Amniotic Sac; Bacteria; Bacterial Vaginosis; Caucasians; Caucasoid Race; Cervix Mucus; Clinical; Collagen; Deletion Mutagenesis; Enzymes; Fetal Membranes; Genes; Genomic DNA; Goals; Health; Infection; Inflammation; Knowledge; Membrane; Mucins; Mucous body substance; Neonatal Mortality; Neuraminidase; Pathogenesis; Play; Pregnancy; Pregnant Women; Premature Birth; Prevalence; Race; Recombinant Proteins; Relative Risks; Risk; Role; Source; Techniques; Term Birth; Testing; Therapeutic Intervention; Time; Tissues; Uterine cavity; Uterus; Vagina; Vaginal Diseases; Virulence; Virulence Factors; Woman; base; collagenase; fetal; gene cloning; genome sequencing; health disparity; in vitro activity; microbiome; mucinase; neonatal morbidity; preterm premature rupture of membranes; protein B

Preterm birth is the leading cause of neonatal morbidity and mortality and the shorter the gestation period, the greater the health concern. The risk for very preterm birth (<32 weeks gestation) in African American women is three times as high as the risk in Caucasian women. Infection of the uterine cavity leads to maternal and/or fetal inflammation and correlates strongly with preterm birth, especially very preterm birth. Vaginal bacteria are a source for intrauterine infections especially in women with bacterial vaginosis (BV) and because the prevalence of BV in African American is twice as high as in Caucasian women, it is likely that BV contributes to the racial disparity in preterm birth. However, as the pathogenesis of BV-associated preterm birth is unknown, the overarching goal of this project is to characterize the pathogenesis. We have evidence that certain bacterial species or sub-species are equipped with virulence factors such as mucinases (e.g. sialidase), and collagenases that contribute to uterine invasion and preterm birth. We hypothesize that mucinases enable traversal of the cervical mucus plug and ascension into the uterus and that collagenases degrade chorionic and amnionic collagen, contributing to invasion and leading to preterm premature rupture of membranes (PPROM). We have evidence that African American race significantly increases the relative risk for vaginal colonization by certain "utero-invasive" bacteria and we hypothesize that this contributes significantly to the racial disparity in preterm birth and preterm premature rupture of membranes. The goals of this project are to identify bacterial virulence determinants that play a role in intrauterine invasion, or the "virulome of infectious preterm birth", and to determine whether colonization by bacteria equipped with this virulome is associated with the elevated risk for preterm birth in African American women.

早产是新生儿发病率和死亡率的主要原因，怀孕期越短，健康问题越大。非裔美国妇女极早产（妊娠<32周）的风险是白人妇女的三倍。子宫腔感染导致母体和/或胎儿炎症，并与早产，特别是极早产密切相关。阴道细菌是子宫内感染的来源，尤其是在患有细菌性阴道病（BV）的女性中，并且由于非洲裔美国人的BV患病率是白人女性的两倍，因此BV可能导致早产的种族差异。然而，由于BV相关早产的发病机制尚不清楚，本项目的总体目标是描述发病机制。我们有证据表明，某些细菌种属或亚种具有毒力因子，如粘蛋白酶（如唾液酸酶）和胶原酶，有助于子宫侵入和早产。我们假设，粘蛋白酶能够穿越宫颈粘液栓并Ascension到子宫，胶原酶降解绒毛膜和绒毛膜胶原，有助于侵袭并导致早产胎膜早破（PPROM）。我们有证据表明，非洲裔美国人的种族显着增加阴道定植的相对风险，某些“子宫侵入”细菌，我们假设，这显着有助于早产和早产胎膜早破的种族差异。该项目的目标是确定细菌毒力决定因素，在子宫内入侵中发挥作用，或“感染性早产的麻烦”，并确定是否由配备了这个麻烦的细菌定植与非裔美国妇女早产的风险升高。