title: Attachment of capsular polysaccharide to the cell wall of Streptococcus pneumoniae type 2 is required for invasive disease.
abstract: The capacity of Streptococcus pneumoniae to produce capsular polysaccharide (CPS) is essential for virulence. The CPS biosynthesis proteins CpsB, CpsC, and CpsD function to regulate CPS production via tyrosine phosphorylation of CpsD. This mechanism of regulating CPS production is important for enabling S. pneumoniae to cause invasive disease. Here, we identify mutations affecting the attachment of CPS to the cell wall. These mutations were located in cpsC, such that CpsC functioned independently from CpsD tyrosine phosphorylation. These mutants produced WT levels of CPS, but were unable to cause bacteremia in mice after intranasal challenge. This finding suggests that cell-wall attachment of CPS is essential for invasive pneumococcal disease; production of WT levels of CPS alone is not sufficient. We also show that cpsB mutants, which lack the phosphotyrosine-protein phosphatase, produced less CPS than the WT strain, but attached substantially more CPS to their cell wall. Thus, the phosphorylated form of CpsD promotes attachment of CPS to the cell wall.
authors.affiliation: School of Molecular and Biomedical Science, University of Adelaide, Adelaide, South Australia 5005, Australia.
authors.forename: Judy K
authors.initials: JK
authors.lastname: Morona
authors.forename: Renato
authors.initials: R
authors.lastname: Morona
authors.forename: James C
authors.initials: JC
authors.lastname: Paton
mesh_terms: D000818:Animals; D001224:Aspartic Acid / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002473:Cell Wall / Q000378:metabolism*; D024881:Drug Resistance, Bacterial / Q000187:drug effects; D004917:Erythromycin / Q000494:pharmacology; D006801:Humans; D008561:Membrane Fusion; D051379:Mice; D009154:Mutation / Q000235:genetics; D011008:Pneumococcal Infections / Q000382:microbiology* / Q000473:pathology*; D011135:Polysaccharides, Bacterial / Q000378:metabolism*; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D013296:Streptococcus pneumoniae / Q000145:classification / Q000166:cytology* / Q000187:drug effects / Q000472:pathogenicity*; D013752:Tetracycline / Q000494:pharmacology; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; C500439:CpsA protein, Streptococcus pneumoniae; D011135:Polysaccharides, Bacterial; D001224:Aspartic Acid; D004917:Erythromycin; C474640:CpsD protein, Streptococcus pneumoniae; D011505:Protein-Tyrosine Kinases; C500440:CpsB protein, Streptococcus pneumoniae; D017027:Protein Tyrosine Phosphatases; D013752:Tetracycline