Abstract
Infection 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.
Highlights
Preterm birth is the leading cause of neonatal mortality worldwide [1]
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
GBS produces small extracellular membrane vesicles (MVs) which are toxic to both fetal and maternal cells
Summary
Preterm birth is the leading cause of neonatal mortality worldwide [1]. Globally, an estimated 13 million babies are born prematurely each year, out of which more than one million succumb to death [2]. Being the leading cause of neonatal death, preterm birth increases the risk of neonatal infections [3]. Epidemiological and clinical studies have shown that colonization of vagina and cervix with GBS significantly increases the probability of intra-amniotic infection, chorio-amnionitis, endometriosis, preterm premature rupture of amniotic membrane (PPROM) and preterm births [10,11,12,13,14,15]. It is postulated that ascending GBS infection from the vagina to the feto-maternal space decreases amniotic membrane integrity causing PPROM [16]. This effect is attributed to the hemolytic pigment of GBS which causes chorio-amnionitis in vivo [17]
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