Mapping the recognition domains of pneumococcal fibronectin-binding proteins PavA and PavB demonstrates a common pattern of molecular interactions with fibronectin type III repeats

Mol Microbiol. 2017 Sep;105(6):839-859. doi: 10.1111/mmi.13740. Epub 2017 Jul 7.

Abstract

Colonization of mucosal respiratory surfaces is a prerequisite for the human pathobiont Streptococcus pneumoniae (the pneumococcus) to cause severe invasive infections. The arsenal of pneumococcal adhesins interacts with a multitude of extracellular matrix proteins. A paradigm for pneumococci is their interaction with the adhesive glycoprotein fibronectin, which facilitates bacterial adherence to host cells. Here, we deciphered the molecular interaction between fibronectin and pneumococcal fibronectin-binding proteins (FnBPs) PavA and PavB respectively. We show in adherence and binding studies that the pneumococcal interaction with fibronectin is a non-human specific trait. PavA and PavB target at least 13 out of 15 type III fibronectin domains as demonstrated in ligand overlay assays, surface plasmon resonance studies and SPOT peptide arrays. Strikingly, both pneumococcal FnBPs recognize similar peptides in targeted type III repeats. Structural comparisons revealed that the targeted type III repeat epitopes cluster on the inner strands of both β-sheets forming the fibronectin domains. Importantly, synthetic peptides of FnIII1 , FnIII5 or FnIII15 bind directly to FnBPs PavA and PavB respectively. In conclusion, our study suggests a common pattern of molecular interactions between pneumococcal FnBPs and fibronectin. The specific epitopes recognized in this study can potentially be tested as antimicrobial targets in further scientific endeavours.

MeSH terms

  • Adhesins, Bacterial / metabolism
  • Bacterial Adhesion / genetics
  • Bacterial Adhesion / physiology
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Carrier Proteins / metabolism
  • Fibronectin Type III Domain / genetics
  • Fibronectin Type III Domain / physiology*
  • Fibronectins / metabolism*
  • Host-Pathogen Interactions
  • Humans
  • Protein Binding / genetics
  • Protein Binding / physiology
  • Protein Domains
  • Streptococcus pneumoniae / metabolism
  • Virulence Factors / metabolism

Substances

  • Adhesins, Bacterial
  • Bacterial Proteins
  • Carrier Proteins
  • FN1 protein, human
  • Fibronectins
  • PavA protein, Streptococcus pneumoniae
  • Virulence Factors