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

• Published in: PLoS pathogens 2016-09, Vol.12 (9), p.e1005816-e1005816
• Main Authors: Surve, Manalee Vishnu, Anil, Anjali, Kamath, Kshama Ganesh, Bhutda, Smita, Sthanam, Lakshmi Kavitha, Pradhan, Arpan, Srivastava, Rohit, Basu, Bhakti, Dutta, Suryendu, Sen, Shamik, Modi, Deepak, Banerjee, Anirban
• Format: Article
• Language: English
• Subjects: Amnion - microbiology; Amnion - pathology; Amniotic Fluid - microbiology; Animals; Apoptosis; Bacteria; Bacterial infections; Bioengineering; Biology and Life Sciences; Cell Line, Tumor; Cellular proteins; Chorioamnionitis - microbiology; Chorioamnionitis - pathology; Cytokines - metabolism; Decidua - microbiology; Decidua - pathology; Disease Models, Animal; Female; Fetal Membranes, Premature Rupture - microbiology; Fetal Membranes, Premature Rupture - pathology; Funding; Health aspects; Humans; Infections; Inflammation; Medicine and Health Sciences; Membranes; Mice; Microscopy; Physiological aspects; Pregnancy; Premature birth; Premature Birth - microbiology; Premature Birth - pathology; Premature infants; Research and analysis methods; Serogroup; Standard deviation; Statistical analysis; Streptococcal Infections - complications; Streptococcal Infections - microbiology; Streptococcal Infections - pathology; Streptococcus; Streptococcus agalactiae - immunology; Streptococcus agalactiae - physiology; Toxins
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1005816

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.