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

早产是新生儿发病率和死亡率的主要原因，妊娠期越短，对健康的担忧越大。非洲裔美国女性早产(怀孕32周)的风险是白人女性的三倍。宫腔感染会导致母亲和/或胎儿的炎症，并与早产，特别是早产密切相关。阴道细菌是宫内感染的来源，特别是在患有细菌性阴道病(BV)的妇女中，由于非裔美国人BV的患病率是高加索妇女的两倍，BV很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，本项目的首要目标是确定其发病机制。我们有证据表明，某些细菌物种或亚种配备了毒力因子，如粘液酶(如唾液酸酶)和胶原酶，它们有助于子宫侵袭和早产。我们假设，粘液酶使宫颈粘液堵塞和上升进入子宫，胶原酶降解绒毛和羊膜胶原，促进侵袭并导致早产胎膜早破(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袭性细菌对阴道定植的相对风险，我们假设这显著地导致了早产和早产胎膜早破的种族差异。该项目的目标是确定在宫内入侵中发挥作用的细菌毒力决定因素，或“感染性早产的毒素体”，并确定配备该毒素体的细菌的定植是否与非裔美国妇女早产风险增加有关。

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.