Multifunctional role of choline binding protein G in pneumococcal pathogenesis

B. Mann, C. Orihuela, J. Antikainen, G. Gao, J. Sublett, T. K. Korhonen, E. Tuomanen

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Abstract

Members of the choline binding protein (Cbp) family are noncovalently bound to phosphorylcholine residues on the surface of Streptococcus pneumoniae. It has been suggested that CbpG plays a role in adherence and increase virulence both at the mucosal surface and in the bloodstream, but the function of this protein has been unclear. A new sequence analysis indicated that CbpG is a possible member of the S1 family of multifunctional surface-associated serine proteases. Clinical isolates contained two alleles of cbpG, and one-third of the strains expressed a truncated protein lacking the C-terminal, cell wall-anchoring choline binding domain. CbpG on the surface of pneumococci (full length) or released into the supernatant (truncated) showed proteolytic activity for fibronectin and casein, as did CbpG expressed on lactobacilli or as a purified full-length or truncated recombinant protein. Recombinant CbpG (rCbpG)-coated beads adhered to eukaryotic cells, and TIGR4 mutants lacking CbpG or having a truncated CbpG protein showed decreased adherence in vitro and attenuation of disease in mouse challenge models of colonization, pneumonia, and bacteremia. Immunization with rCbpG was protective in an animal model of colonization and sepsis. We propose that CbpG is a multifunctional surface protein that in the cell-attached or secreted form cleaves host extracellular matrix and in the cell-attached form participates in bacterial adherence. This is the first example of distinct functions in virulence that are dependent on natural variation in expression of a choline binding domain.

Original languageEnglish (US)
Pages (from-to)821-829
Number of pages9
JournalInfection and immunity
Volume74
Issue number2
DOIs
StatePublished - Feb 1 2006

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ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

Cite this

Mann, B., Orihuela, C., Antikainen, J., Gao, G., Sublett, J., Korhonen, T. K., & Tuomanen, E. (2006). Multifunctional role of choline binding protein G in pneumococcal pathogenesis. Infection and immunity, 74(2), 821-829. https://doi.org/10.1128/IAI.74.2.821-829.2006