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

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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.