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- Title
The Streptococcus agalactiae cell wall‐anchored protein PbsP mediates adhesion to and invasion of epithelial cells by exploiting the host vitronectin/α<sub>v </sub>integrin axis.
- Authors
De Gaetano, Giuseppe Valerio; Pietrocola, Giampiero; Romeo, Letizia; Galbo, Roberta; Lentini, Germana; Giardina, Miriam; Biondo, Carmelo; Midiri, Angelina; Mancuso, Giuseppe; Venza, Mario; Venza, Isabella; Firon, Arnaud; Trieu‐Cuot, Patrick; Teti, Giuseppe; Speziale, Pietro; Beninati, Concetta
- Abstract
Summary: Binding of microbial pathogens to host vitronectin (Vtn) is a common theme in the pathogenesis of invasive infections. In this study, we characterized the role of Vtn in the invasion of mucosal epithelial cells by Streptococcus agalactiae (i.e. group B streptococcus or GBS), a frequent human pathogen. Moreover, we identified PbsP, a previously described plasminogen‐binding protein of GBS, as a dual adhesin that can also interact with human Vtn through its streptococcal surface repeat (SSURE) domains. Deletion of the pbsP gene decreases both bacterial adhesion to Vtn‐coated inert surfaces and the ability of GBS to interact with epithelial cells. Bacterial adherence to and invasion of epithelial cells were either inhibited or enhanced by cell pretreatment with, respectively, anti‐Vtn antibodies or Vtn, confirming the role of Vtn as a GBS ligand on host cells. Finally, antibodies directed against the integrin αv subunit inhibited Vtn‐dependent cell invasion by GBS. Collectively, these results indicate that Vtn acts as a bridge between the SSURE domains of PbsP on the GBS surface and host integrins to promote bacterial invasion of epithelial cells. Therefore, inhibition of interactions between PbsP and extracellular matrix components could represent a viable strategy to prevent colonization and invasive disease by GBS. The mechanisms by which the bacterial pathogen group B streptococcus (GBS) interacts with host cells are incompletely understood. We show here that the extracellular matrix protein vitronectin acts as a bridge between the bacterial cell wall protein PbsP and integrins present on the host cell membrane. These interactions enable GBS to adhere to epithelial cells and invade them. Drugs or antibodies capable of blocking these interactions may be useful to control infections by GBS.
- Subjects
STREPTOCOCCUS agalactiae; EPITHELIAL cells; CELL adhesion; VITRONECTIN; INTEGRINS
- Publication
Molecular Microbiology, 2018, Vol 110, Issue 1, p82
- ISSN
0950-382X
- Publication type
Article
- DOI
10.1111/mmi.14084