title: 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.
authors.affiliation: Department of Pediatrics and Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC.
authors.forename: Kimberly F
authors.identifier: http://orcid.org/0000-0002-0101-7969
authors.initials: KF
authors.lastname: Starr
authors.affiliation: Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Porsch
authors.affiliation: Department of Pediatrics and Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC.
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Seed
authors.affiliation: Complex Carbohydrate Research Center, University of Georgia, Athens, GA.
authors.forename: Christian
authors.initials: C
authors.lastname: Heiss
authors.affiliation: Complex Carbohydrate Research Center, University of Georgia, Athens, GA.
authors.forename: Radnaa
authors.initials: R
authors.lastname: Naran
authors.affiliation: Complex Carbohydrate Research Center, University of Georgia, Athens, GA.
authors.forename: L Scott
authors.identifier: http://orcid.org/0000-0002-6905-2760
authors.initials: LS
authors.lastname: Forsberg
authors.affiliation: Radiation Oncology, Chaim Sheba Medical Center, Ramat Gan, Israel.
authors.forename: Uri
authors.initials: U
authors.lastname: Amit
authors.affiliation: Soroka University Medical Center, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Pablo
authors.initials: P
authors.lastname: Yagupsky
authors.affiliation: Complex Carbohydrate Research Center, University of Georgia, Athens, GA.
authors.forename: Parastoo
authors.initials: P
authors.lastname: Azadi
authors.affiliation: Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA.|University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
authors.forename: Joseph W
authors.initials: JW
authors.lastname: St Geme
mesh_terms: D016667:Bacterial Capsules / Q000737:chemistry*; D001426:Bacterial Proteins / Q000737:chemistry*; D002850:Chromatography, Gel; D008401:Gas Chromatography-Mass Spectrometry; D005798:Genes, Bacterial; D016695:Glycosyltransferases / Q000235:genetics; D017882:Kingella kingae / Q000235:genetics / Q000472:pathogenicity*; D016870:Neisseriaceae Infections / Q000473:pathology*; D011135:Polysaccharides, Bacterial / Q000737:chemistry*; D014774:Virulence / Q000502:physiology
chemical_list: D001426:Bacterial Proteins; D011135:Polysaccharides, Bacterial; D016695:Glycosyltransferases