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

早产是新生儿发病和死亡的主要原因，妊娠期越短，健康问题越严重。非裔美国妇女发生极早产（妊娠<32周）的风险是白种人妇女的三倍。子宫腔感染可导致母体和/或胎儿炎症，并与早产，特别是非常早产密切相关。阴道细菌是宫内感染的一个来源，特别是在患有细菌性阴道病（BV）的妇女中，由于BV在非洲裔美国妇女中的患病率是白人妇女的两倍，因此BV很可能导致了早产的种族差异。然而，由于bv相关早产的发病机制尚不清楚，本项目的首要目标是表征其发病机制。我们有证据表明，某些细菌种类或亚种具有毒力因子，如粘液酶（如唾液酸酶）和胶原酶，这些毒力因子有助于子宫侵入和早产。我们推测，黏液酶使宫颈黏液塞穿过并上升到子宫，而胶原酶降解绒毛膜和羊膜胶原，有助于侵入并导致胎膜早破（PPROM）。我们有证据表明，非裔美国人种族显著增加了某些“子宫侵入性”细菌在阴道定植的相对风险，我们假设这在很大程度上导致了早产和胎膜早破的种族差异。该项目的目标是确定在宫内侵入或“感染性早产病毒组”中起作用的细菌毒力决定因素，并确定配备该病毒组的细菌定植是否与非裔美国妇女早产风险升高有关。

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.