The Streptococcus pneumoniae adhesin PsrP binds to Keratin 10 on lung cells
Open Access
- 7 August 2009
- journal article
- Published by Wiley in Molecular Microbiology
- Vol. 73 (4), 663-679
- https://doi.org/10.1111/j.1365-2958.2009.06796.x
Abstract
Pneumococcal serine-rich repeat protein (PsrP) is a pathogenicity island-encoded adhesin that mediates attachment to lung cells. It is a member of the serine-rich repeat protein family and the largest bacterial protein known. PsrP production by S. pneumoniae was confirmed by immunoblotting and a truncated version of the protein was determined to be glycosylated. Using isogenic psrP mutants complemented with various PsrP constructs and competitive inhibition assays with recombinant proteins, we determined that PsrP requires an extended SRR2 domain for function and that adhesion is mediated through amino acids 273–341 of its basic region (BR) domain. Affinity chromatography, immunoprecipitation, enzyme-linked immunosorbent assay (ELISA), fluorescent-activated cell sorting (FACS) and immunofluorescent colocalization studies determined that PsrP binds to Keratin 10 (K10) on the surface of lung but not nasopharyngeal epithelial cells. Unglycosylated K10 bound to wild type but not psrP deficient pneumococci; suggesting that unlike other serine-rich repeat proteins, PsrP-mediated adhesion is independent of lectin activity. Finally, mice immunized with recombinant (r)PsrPBR had significantly less bacteria in their blood and improved survival versus controls following intranasal challenge. We conclude that the BR domain of PsrP binds to K10 in a lectin-independent manner, that K10 is expressed on lung cells and that vaccination with rPsrPBR is protective against pneumococcal disease.Keywords
This publication has 56 references indexed in Scilit:
- Laminin receptor initiates bacterial contact with the blood brain barrier in experimental meningitis modelsJCI Insight, 2009
- The Group B Streptococcal Serine‐Rich Repeat 1 Glycoprotein Mediates Penetration of the Blood‐Brain BarrierThe Journal of Infectious Diseases, 2009
- Role of the serine-rich surface glycoprotein GspB of Streptococcus gordonii in the pathogenesis of infective endocarditisMicrobial Pathogenesis, 2008
- Population Snapshot of EmergentStreptococcus pneumoniaeSerotype 19A in the United States, 2005The Journal of Infectious Diseases, 2008
- National and Regional Assessment of Antimicrobial Resistance among Community-Acquired Respiratory Tract Pathogens Identified in a 2005-2006 U.S. Faropenem Surveillance StudyAntimicrobial Agents and Chemotherapy, 2007
- The Surface Protein Srr-1 of Streptococcus agalactiae Binds Human Keratin 4 and Promotes Adherence to Epithelial HEp-2 CellsInfection and Immunity, 2007
- Emergence of a Multiresistant Serotype 19A Pneumococcal Strain Not Included in the 7-Valent Conjugate Vaccine as an Otopathogen in ChildrenPublished by American Medical Association (AMA) ,2007
- Identification of a Candidate Streptococcus pneumoniae Core Genome and Regions of Diversity Correlated with Invasive Pneumococcal DiseaseInfection and Immunity, 2006
- New consensus nomenclature for mammalian keratinsThe Journal of cell biology, 2006
- Gapped BLAST and PSI-BLAST: a new generation of protein database search programsNucleic Acids Research, 1997