Membrane Vesicles of Group B Streptococcus Disrupt Feto-Maternal Barrier Leading to Preterm Birth

Citation: Surve MV, Anil A, Kamath KG, Bhutda S, Sthanam LK, Pradhan A, et al. (2016) Membrane Vesicles of Group B Streptococcus Disrupt Feto-Maternal Barrier Leading to Preterm Birth. PLoS Pathog 12(9): e1005816. doi:10.1371/journal.ppat.1005816
Published: September 1, 2016

Abstract
streptococcus_agalactiae-tifInfection of the genitourinary tract with Group B Streptococcus (GBS), an opportunistic gram positive pathogen, is associated with premature rupture of amniotic membrane and preterm birth. In this work, we demonstrate that GBS produces membrane vesicles (MVs) in a serotype independent manner. These MVs are loaded with virulence factors including extracellular matrix degrading proteases and pore forming toxins. Mice chorio-decidual membranes challenged with MVs ex vivo resulted in extensive collagen degradation leading to loss of stiffness and mechanical weakening. MVs when instilled vaginally are capable of anterograde transport in mouse reproductive tract. Intra-amniotic injections of GBS MVs in mice led to upregulation of pro-inflammatory cytokines and inflammation mimicking features of chorio-amnionitis; it also led to apoptosis in the chorio-decidual tissue. Instillation of MVs in the amniotic sac also resulted in intrauterine fetal death and preterm delivery. Our findings suggest that GBS MVs can independently orchestrate events at the feto-maternal interface causing chorio-amnionitis and membrane damage leading to preterm birth or fetal death.

Author Summary: Preterm birth is a major health concern globally as it is not only a leading cause of neonatal death, but also has long term consequences including defective brain development. Infection of vagina and cervix of pregnant women with the bacteria, Group B Streptococcus (GBS), causes chorio-amnionitis that significantly increases the probability of preterm births. We report that, GBS produces small extracellular membrane vesicles (MVs) which are toxic to both fetal and maternal cells. In animal studies, we found that the MVs disrupt the connective tissue of the fetal membrane reducing its mechanical strength which may cause premature rupture of amniotic sac. Further we show that even in absence of the bacteria, the MVs directly led to extensive inflammation in the mouse resulting in chorio-amnionitis, preterm births and still births. Collectively, our findings reveal how GBS while colonizing the lower genitourinary tract might orchestrate events at the fetal membrane leading to premature birth.

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