Causal relationship between capsule types and virulence phenotypes. (A) Schematic illustration of the capsule-switching scheme. The cps gene clusters of target (recipient) strains were first replaced with JC to produce unencapsulated mutants, which were then transformed with the cps gene amplicons of donor strains to yield capsule replacement strains. Selected HV (red symbols) and LV (green symbols) serotypes are indicated below. (B) The levels of survival (left) and bacteremia (right) of CD1 mice infected i.p. with 10⁴ CFU of the isogenic capsule variants generated in serotype 6A strain TH870^6A. n = 5–6. (C) Same as B except for using the isogenic variants of serotype 6B strain TH2919^6B. n = 5–6. (D) The differences in the sequence of wciP and CPS repeating unit between serotypes 6A and 6B. The polymorphic nucleotide and corresponding amino acid sequences of wciP and linkage between rhamnose and ribitol-5-phosphate in serotypes 6A and 6B are depicted. Glc, glucose; Gal, galactose; Rha, rhamnose; R-5-P, ribitol-5-phosphate. (E) Same as B except for using the isogenic strains with reciprocal single nucleotide polymorphism (SNP) switches in the TH870^6A and TH2919^6B backgrounds. n = 5. (F and G) The levels of survival (F) and bacteremia (G) of CD1 mice after i.t. infection with 10⁷ CFU of the isogenic strains. n = 5. All data were pooled from two independent experiments.