title: Membrane Vesicles of Group B Streptococcus Disrupt Feto-Maternal Barrier Leading to Preterm Birth.
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.
authors: Dept. of Biosciences and Bioengineering, Indian Institute of Technology-Bombay, Mumbai, India.
authors: Manalee Vishnu
authors: MV
authors: Surve
authors: Dept. of Biosciences and Bioengineering, Indian Institute of Technology-Bombay, Mumbai, India.
authors: Anjali
authors: A
authors: Anil
authors: Dept. of Biosciences and Bioengineering, Indian Institute of Technology-Bombay, Mumbai, India.
authors: Kshama Ganesh
authors: KG
authors: Kamath
authors: Dept. of Biosciences and Bioengineering, Indian Institute of Technology-Bombay, Mumbai, India.
authors: Smita
authors: S
authors: Bhutda
authors: Dept. of Biosciences and Bioengineering, Indian Institute of Technology-Bombay, Mumbai, India.
authors: Lakshmi Kavitha
authors: LK
authors: Sthanam
authors: Dept. of Biosciences and Bioengineering, Indian Institute of Technology-Bombay, Mumbai, India.
authors: Arpan
authors: 0000-0003-3924-745X
authors: A
authors: Pradhan
authors: Dept. of Biosciences and Bioengineering, Indian Institute of Technology-Bombay, Mumbai, India.
authors: Rohit
authors: R
authors: Srivastava
authors: Molecular Biology Division, Bhabha Atomic Research Centre, Mumbai, India.
authors: Bhakti
authors: B
authors: Basu
authors: Dept. of Earth Sciences, Indian Institute of Technology-Bombay, Mumbai, India.
authors: Suryendu
authors: S
authors: Dutta
authors: Dept. of Biosciences and Bioengineering, Indian Institute of Technology-Bombay, Mumbai, India.
authors: Shamik
authors: S
authors: Sen
authors: Molecular and Cellular Biology Laboratory, National Institute for Research in Reproductive Health (ICMR), Mumbai, India.
authors: Deepak
authors: D
authors: Modi
authors: Dept. of Biosciences and Bioengineering, Indian Institute of Technology-Bombay, Mumbai, India.
authors: Anirban
authors: 0000-0002-4229-5981
authors: A
authors: Banerjee
mesh_terms: D000650:Amnion / Q000382:microbiology / Q000473:pathology; D000653:Amniotic Fluid / Q000382:microbiology; D000818:Animals; D045744:Cell Line, Tumor; D002821:Chorioamnionitis / Q000382:microbiology / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D003656:Decidua / Q000382:microbiology / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D005322:Premature Rupture of Fetal Membranes / Q000382:microbiology* / Q000473:pathology; D006801:Humans; D007249:Inflammation; D051379:Mice; D011247:Pregnancy; D047928:Premature Birth / Q000382:microbiology* / Q000473:pathology; D065288:Serogroup; D013290:Streptococcal Infections / Q000150:complications / Q000382:microbiology* / Q000473:pathology; D013292:Streptococcus agalactiae / Q000276:immunology / Q000502:physiology*
chemical_list: D016207:Cytokines