Project 454195

Preterm birth affects 8% of pregnancies in Canada and is a leading cause of infant and child death worldwide. Preterm birth can lead to severe neurological disorders and breathing problems in children as well as financial and emotional stress for families. While there are multiple causes of preterm birth, up to 60% of cases arise from bacterial infection in the uterus. In particular, the presence of select vaginal bacteria correlates with increased risk for preterm birth. These bacteria can invade the uterus and infect pregnancy tissues, which can lead to severe infection of the mother or baby, early membrane rupture (water breaking), spontaneous abortion and preterm labour. However, we do not know how these bacteria affect the uterus and contribute to pregnancy complications. Notably, antibiotics do not stop infection-induced preterm labour nor improve outcomes. Furthermore, current predictive tests detect less than 50% of cases. Thus, there is a dire need to understand how vaginal bacteria trigger infection-induced preterm labour. Protein degradation (also known as proteolysis) is a central feature of labour induction. Proteolysis can alter regulatory pathways and remodel pregnancy tissues to trigger key events in the birth process such as cervical dilation, fetal membrane rupture (water breaking) and uterine contractions. However, incorrectly timed proteolysis can prematurely trigger these processes and initiate preterm labour. Our data demonstrate that vaginal bacteria secrete proteolytic enzymes that break down structural and regulatory components found in pregnancy tissues. I will investigate how vaginal bacteria and their proteolytic enzymes modulate pregnancy tissues to trigger fetal membrane rupture, uterine contractions and premature labour. This work will improve our knowledge of infection-induced preterm labour and uncover novel targets for diagnosis and treatment.