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Structure-Function Characterization of Streptococcus intermedius Surface Antigen Pas.

Joshua L Mieher1, Norbert Schormann1, Ren Wu1

  • 1Department of Biochemistry and Molecular Genetics, University of Alabama at Birminghamgrid.265892.2, Birmingham, Alabama, USA.

Journal of Bacteriology
|August 2, 2021
PubMed
Summary
This summary is machine-generated.

Streptococcus intermedius surface protein Pas aids in host and microbial interactions. It binds to lung proteins and enhances pathogen biofilms, potentially influencing disease outcomes.

Keywords:
Candida albicansStreptococcus intermediusprotein structure-functionsurface antigens

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Area of Science:

  • Microbiology
  • Structural Biology
  • Infectious Diseases

Background:

  • Streptococcus intermedius, an oral commensal, is implicated in various infections, including cystic fibrosis lung disease.
  • Surface proteins mediate bacterial adhesion, biofilm formation, and colonization.
  • The antigen I/II (AgI/II) family adhesin Pas is a key surface protein in S. intermedius.

Purpose of the Study:

  • To structurally and functionally characterize the S. intermedius adhesin Pas.
  • To investigate Pas's role in microbial-host and interkingdom interactions.
  • To determine Pas's contribution to biofilm formation with opportunistic pathogens.

Main Methods:

  • Crystal structure determination of VPas and C123Pas domains.
  • Affinity measurements for Pas interactions with host proteins (Gp340, fibrinogen).
  • Dual-species biofilm assays with Candida albicans and Pseudomonas aeruginosa using wild-type and mutant S. intermedius strains.

Main Results:

  • The crystal structures of VPas and C123Pas reveal similarities to other AgI/II adhesins, with conserved metal-binding sites.
  • Pas exhibits high-affinity binding to lung alveolar glycoprotein 340 (Gp340) and fibrinogen.
  • Pas-deficient S. intermedius showed reduced dual-species biofilm formation with Candida albicans but not Pseudomonas aeruginosa.

Conclusions:

  • Pas plays a significant role in both microbial-host interactions (binding Gp340, fibrinogen) and interkingdom microbial interactions (enhancing C. albicans biofilms).
  • These interactions mediated by Pas may contribute to S. intermedius colonization and pathogenesis in polymicrobial infections.
  • Pas represents a potential therapeutic target for managing S. intermedius-associated diseases.