Binding of Glycoprotein Srr1 of Streptococcus agalactiae to Fibrinogen Promotes Attachment to Brain Endothelium and the Development of Meningitis

Ho Seong Seo; Rong Mu; Kim, Brandon J.; Doran, Kelly S.; Sullam, Paul M.
October 2012
PLoS Pathogens;Oct2012, Vol. 8 Issue 10, Special section p1
Academic Journal
The serine-rich repeat glycoprotein Srr1 of Streptococcus agalactiae (GBS) is thought to be an important adhesin for the pathogenesis of meningitis. Although expression of Srr1 is associated with increased binding to human brain microvascular endothelial cells (hBMEC), the molecular basis for this interaction is not well defined. We now demonstrate that Srr1 contributes to GBS attachment to hBMEC via the direct interaction of its binding region (BR) with human fibrinogen. When assessed by Far Western blotting, Srr1 was the only protein in GBS extracts that bound fibrinogen. Studies using recombinant Srr1-BR and purified fibrinogen in vitro confirmed a direct protein-protein interaction. Srr1-BR binding was localized to amino acids 283-410 of the fibrinogen Aα chain. Structural predictions indicated that the conformation of Srr1-BR is likely to resemble that of SdrG and other related staphylococcal proteins that bind to fibrinogen through a "dock, lock, and latch" mechanism (DLL). Deletion of the predicted latch domain of Srr1-BR abolished the interaction of the BR with fibrinogen. In addition, a mutant GBS strain lacking the latch domain exhibited reduced binding to hBMEC, and was significantly attenuated in an in vivo model of meningitis. These results indicate that Srr1 can bind fibrinogen directly likely through a DLL mechanism, which has not been described for other streptococcal adhesins. This interaction was important for the pathogenesis of GBS central nervous system invasion and subsequent disease progression.


Related Articles

  • Evidence for the Sialylation of PilA, the PI-2a Pilus-Associated Adhesin of Streptococcus agalactiae Strain NEM316. Morello, Eric; Mallet, Adeline; Konto-Ghiorghi, Yoan; Chaze, Thibault; Mistou, Michel-Yves; Oliva, Giulia; Oliveira, Liliana; Di Guilmi, Anne-Marie; Trieu-Cuot, Patrick; Dramsi, Shaynoor // PLoS ONE;9/25/2015, Vol. 10 Issue 9, p1 

    Streptococcus agalactiae (or Group B Streptococcus, GBS) is a commensal bacterium present in the intestinal and urinary tracts of approximately 30% of humans. We and others previously showed that the PI-2a pilus polymers, made of the backbone pilin PilB, the tip adhesin PilA and the cell wall...

  • The enhancement of biofilm formation in Group B streptococcal isolates at vaginal pH. Ho, Yueh-Ren; Li, Chien-Ming; Yu, Chen-Hsiang; Lin, Yuh-Jyh; Wu, Ching-Ming; Harn, I-Chen; Tang, Ming-Jer; Chen, Yi-Ting; Shen, Fang-Chi; Lu, Chien-Yi; Tsai, Tai-Chun; Wu, Jiunn-Jong // Medical Microbiology & Immunology;Apr2013, Vol. 202 Issue 2, p105 

    Group B streptococcus (GBS) is a common asymptomatic colonizer in acidic vagina of pregnant women and can transmit to newborns, causing neonatal pneumonia and meningitis. Biofilm formation is often associated with bacterial colonization and pathogenesis. Little is known about GBS biofilm and the...

  • Group B Streptococcal Infection and Activation of Human Astrocytes. Stoner, Terri D.; Weston, Thomas A.; Trejo, JoAnn; Doran, Kelly S. // PLoS ONE;Jun2015, Vol. 10 Issue 6, p1 

    Background: Streptococcus agalactiae (Group B Streptococcus, GBS) is the leading cause of life-threatening meningitis in human newborns in industrialized countries. Meningitis results from neonatal infection that occurs when GBS leaves the bloodstream (bacteremia), crosses the blood-brain...

  • Genetic islands of Streptococcus agalactiae strains NEM316 and 2603VR and their presence in other Group B Streptococcal strains. Herbert, Mark A.; Beveridge, Catriona J.E.; McCormick, David; Aten, Emmelien; Jones, Nicola; Snyder, Lori A.S.; Saunders, Nigel J. // BMC Microbiology;2005, Vol. 5, p1 

    Background: Streptococcus agalactiae (Group B Streptococcus; GBS) is a major contributor to obstetric and neonatal bacterial sepsis. Serotype III strains cause the majority of late-onset sepsis and meningitis in babies, and thus appear to have an enhanced invasive capacity compared with the...

  • The Biology of Neisseria Adhesins. Miao-Chiu Hung; Christodoulides, Myron // Biology (2079-7737);Sep2013, Vol. 2 Issue 3, p1054 

    Members of the genus Neisseria include pathogens causing important human diseases such as meningitis, septicaemia, gonorrhoea and pelvic inflammatory disease syndrome. Neisseriae are found on the exposed epithelia of the upper respiratory tract and the urogenital tract. Colonisation of these...

  • Fenotis y mecanismo de resistencia a macrólidos y lincosamidas en aislados de Streptococcus agalactiae con significación clinica en un preriodo de ocho años (2002-2010). Campelo, Fernando Artiles; Pedrosa, Ana Cañas; Antúnez, Isabel Álamo; Capuz, Bernardo Lafarga // Revista Española de Quimioterapia;mar2012, Vol. 25 Issue 1, p42 

    Introduction. Streptococcus agalactiae is the most prevalent agent of invasive disease in the newborn (sepsis, pneumonia, and meningitis), as well as an important cause of puerperal fever, urinary tract infection and surgical site infection. The aim of our study was to know the evolution of...

  • Intrapartum GBS prophylaxis does not prevent long-term morbidity of GBS meningitis. Fisher, Staccy L.; Richards, Cassandra A.; Volansky, Rob; Zacharyczuk, Colleen // Infectious Diseases in Children;Nov2011, Vol. 24 Issue 11, p17 

    The article discusses a study which assessed the outcomes of group B streptoccocal meningitis in infants.

  • The GBS PI-2a Pilus Is Required for Virulence in Mice Neonates. Papasergi, Salvatore; Brega, Sara; Mistou, Michel-Yves; Firon, Arnaud; Oxaran, Virginie; Dover, Ron; Teti, Giuseppe; Yechiel Shai; Trieu-Cuot, Patrick; Dramsi, Shaynoor // PLoS ONE;2011, Vol. 6 Issue 4, p1 

    Background: Streptococcus agalactiae (Group B Streptococcus) is a leading cause of sepsis and meningitis in newborns. Most bacterial pathogens, including gram-positive bacteria, have long filamentous structures known as pili extending from their surface. Although pili are described as adhesive...

  • Maternal Antibody at Delivery Protects Neonates From Early Onset Group B Streptococcal Disease. Baker, Carol J.; Carey, Vincent J.; Rench, Marcia A.; Edwards, Morven S.; Hillier, Sharon L.; Kasper, Dennis L.; Platt, Richard // Journal of Infectious Diseases;Mar2014, Vol. 209 Issue 5, p781 

    Background. Further reduction in the group B streptococcal (GBS) disease burden in neonates in the United States awaits an additional prevention strategy, such as maternal immunization.Methods. We performed a prospective, multicenter, case-control study of 33 mothers delivering neonates with...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics