title: The effect that mutations in the conserved capsular polysaccharide biosynthesis genes cpsA, cpsB, and cpsD have on virulence of Streptococcus pneumoniae.
abstract: Four genes, cpsA-cpsD, at the 5' end of the capsular polysaccharide (CPS) biosynthesis locus are conserved in nearly all of the 90 known serotypes of Streptococcus pneumoniae. In the present study, the impact that mutations in cpsA, cpsB, and cpsD have on CPS production and on virulence in mice infected via systemic and intranasal routes was investigated. Strains exhibiting rough colony morphologies (in which either the cpsB or cpsD gene had been deleted) were avirulent, but a smooth, partially encapsulated strain (in which the cpsA gene had been deleted) was as virulent as the wild-type strain. Interestingly, mucoid strains containing mutations affecting the [YGX](3)-repeat domain of CpsD were unable to cause bacteremia after intranasal challenge of CD1 mice, even though such strains were capable of killing BALB/c mice after intraperitoneal challenge. In our model, the ability of S. pneumoniae to regulate, via CpsD phosphorylation, CPS production was required for its transition from the lung to the bloodstream.
authors.affiliation: School of Molecular and Biomedical Science, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Judy K
authors.initials: JK
authors.lastname: Morona
authors.forename: David C
authors.initials: DC
authors.lastname: Miller
authors.forename: Renato
authors.initials: R
authors.lastname: Morona
authors.forename: James C
authors.initials: JC
authors.lastname: Paton
mesh_terms: D000818:Animals; D016667:Bacterial Capsules / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D016254:Mutagenesis, Insertional; D011018:Pneumonia, Pneumococcal / Q000382:microbiology*; D011135:Polysaccharides, Bacterial / Q000096:biosynthesis / Q000235:genetics*; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics*; D018709:Statistics, Nonparametric; D013296:Streptococcus pneumoniae / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity*; D016019:Survival Analysis; D014774:Virulence
chemical_list: D011135:Polysaccharides, Bacterial; C474640:CpsD protein, Streptococcus pneumoniae; D011505:Protein-Tyrosine Kinases