The Streptococcus agalactiae cell wall-anchored protein PbsP mediates adhesion to and invasion of epithelial cells by exploiting the host vitronectin/αv integrin axis

Giuseppe Valerio De Gaetano, Giampiero Pietrocola, Letizia Romeo, Roberta Galbo, Germana Lentini, Miriam Giardina, Carmelo Biondo, Angelina Midiri, Giuseppe Mancuso, Mario Venza, Isabella Venza, Arnaud Firon, Patrick Trieu-Cuot, Giuseppe Teti, Pietro Speziale, Concetta Beninati

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)82-94
Number of pages13
JournalMolecular Microbiology
Volume110
Issue number1
DOIs
Publication statusPublished - Oct 2018

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