Kingella kingae Expresses Four Structurally Distinct Polysaccharide Capsules That Differ in Their Correlation with Invasive Disease

Abstract

Kingella kingae is an encapsulated gram-negative organism that is a common cause of osteoarticular infections in young children. In earlier work, we identified a glycosyltransferase gene called csaA that is necessary for synthesis of the [3)-β-GalpNAc-(1→5)-β-Kdop-(2→] polysaccharide capsule (type a) in K. kingae strain 269–492. In the current study, we analyzed a large collection of invasive and carrier isolates from Israel and found that csaA was present in only 47% of the isolates. Further examination of this collection using primers based on the sequence that flanks csaA revealed three additional gene clusters (designated the csb, csc, and csd loci), all encoding predicted glycosyltransferases. The csb locus contains the csbA, csbB, and csbC genes and is associated with a capsule that is a polymer of [6)-α-GlcpNAc-(1→5)-β-(8-OAc)Kdop-(2→] (type b). The csc locus contains the cscA, cscB, and cscC genes and is associated with a capsule that is a polymer of [3)-β-Ribf-(1→2)-β-Ribf-(1→2)-β-Ribf-(1→4)-β-Kdop-(2→] (type c). The csd locus contains the csdA, csdB, and csdC genes and is associated with a capsule that is a polymer of [P-(O→3)[β-Galp-(1→4)]-β-GlcpNAc-(1→3)-α-GlcpNAc-1-] (type d). Introduction of the csa, csb, csc, and csd loci into strain KK01Δcsa, a strain 269–492 derivative that lacks the native csaA gene, was sufficient to produce the type a capsule, type b capsule, type c capsule, and type d capsule, respectively, indicating that these loci are solely responsible for determining capsule type in K. kingae. Further analysis demonstrated that 96% of the invasive isolates express either the type a or type b capsule and that a disproportionate percentage of carrier isolates express the type c or type d capsule. These results establish that there are at least four structurally distinct K. kingae capsule types and suggest that capsule type plays an important role in promoting K. kingae invasive disease.

Kingella kingae Surface Polysaccharides Promote Resistance to Human Serum and Virulence in a Juvenile Rat Model

“…The polysaccharide capsules of Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis, and a variety of other organisms have been extensively studied due to their importance as virulence factors and their effective use as vaccine antigens (15)(16)(17)(18). In K. kingae, four distinct polysaccharide capsules, designated types a, b, c, and d, have been identified (19). Capsule types a and b account for greater than 95% of invasive disease isolates (19,20).…”

“…In K. kingae, four distinct polysaccharide capsules, designated types a, b, c, and d, have been identified (19). Capsule types a and b account for greater than 95% of invasive disease isolates (19,20). Previous work has demonstrated that the capsule is required for full K. kingae virulence in a juvenile rat model of invasive disease (21,22).…”

Phasevarion-Regulated Virulence in the Emerging Pediatric Pathogen Kingella kingae

“…The major virulence factor is RtxA, a toxin that has been shown to play a key role in virulence in an animal model of infection and allows the bacteria to breach the respiratory tract and joints (10,11). The second is capsule that is speculated, based on the role of other encapsulated bacteria, to protect the bacterium from the host immune response and to enable mucosal colonization, survival of the organism in the bloodstream, and invasion of deep body sites (12)(13)(14)(15). The other suggested K. kingae virulence factors, which have yet to be studied in an in vivo model of infection, include type IV pili that mediate possible initial adherence (16), KnnH, an adhesin allowing possible respiratory tract attachment (12), and outer membrane vesicles produced during infection that may offer a strategic advantage in breaching the respiratory epithelium (17).…”

Investigation of Kingella kingae Invasive Infection Outbreaks in Day Care Facilities: Assessment of a Rapid Genotyping Tool Targeting the DNA Uptake Sequence

“…The K. kingae strains carried differ in virulence. Some strains belonging to a few distinct genotypic clones and characterized by polysaccharide capsule a or b are responsible for the vast majority of clinical diseases (11). On the other hand, other clones that elaborate capsule type c or d are usually found as mere respiratory colonizers and are rarely isolated from invasive infections (11).…”

“…Some strains belonging to a few distinct genotypic clones and characterized by polysaccharide capsule a or b are responsible for the vast majority of clinical diseases (11). On the other hand, other clones that elaborate capsule type c or d are usually found as mere respiratory colonizers and are rarely isolated from invasive infections (11). The age-related prevalence of K. kingae colonization parallels that of invasive disease, reaching 10 to 12% during the second year of life and decreasing in older children (4,5).…”