Membrane Vesicles of Group B Streptococcus Disrupt Feto-Maternal Barrier Leading to Preterm Birth |
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Authors: | Manalee Vishnu Surve Anjali Anil Kshama Ganesh Kamath Smita Bhutda Lakshmi Kavitha Sthanam Arpan Pradhan Rohit Srivastava Bhakti Basu Suryendu Dutta Shamik Sen Deepak Modi Anirban Banerjee |
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Affiliation: | 1 Dept. of Biosciences and Bioengineering, Indian Institute of Technology-Bombay, Mumbai, India, ; 2 Molecular Biology Division, Bhabha Atomic Research Centre, Mumbai, India, ; 3 Dept. of Earth Sciences, Indian Institute of Technology-Bombay, Mumbai, India, ; 4 Molecular and Cellular Biology Laboratory, National Institute for Research in Reproductive Health (ICMR), Mumbai, India, ; University of California, San Francisco, UNITED STATES, |
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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. |
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