# Pathogenicity of the emerging pathogen Kingella kingae

> **NIH NIH R01** · CHILDREN'S HOSP OF PHILADELPHIA · 2024 · $445,000

## Abstract

Kingella kingae is an invasive gram-negative pathogen that has been recognized recently as a leading cause
of bone and joint infections in young children, accounting for up to 88% of osteoarticular cases in children <4
years old. In addition, K. kingae is an important cause of invasive bloodstream infections in young children.
Complications of osteoarticular infections in children include abnormalities in bone growth, limitation of joint
mobility, unstable joint articulation, and chronic joint dislocation, resulting in residual skeletal dysfunction in 10-
25% of cases. Complications of invasive bloodstream infections include multi-organ injury and mortality.
Approximately 25% of K. kingae isolates possess β-lactamase activity, and many of these isolates are
resistant to other antibiotics as well, raising concern about approaches to treatment in the future. At present
there are no effective strategies to prevent K. kingae disease and the associated morbidity. The pathogenesis
of K. kingae disease begins with colonization of the oropharynx, followed by invasion of the bloodstream and
spread to bones, joints, and other sites. We have established that isolates of K. kingae produce an
exopolysaccharide that is encoded by the pamABCDE locus, is a homopolymer of galactofuranose, is secreted
from the organism, and is a critical virulence factor essential for full virulence. We have found that there are 2
distinct exopolysaccharide structures, distinguished by the linkage of the galactofuranose repeating subunit
and referred to as type 1 and type 2. Importantly, the exopolysaccharide promotes resistance to serum-
mediated killing and neutrophil phagocytosis and thereby promotes K. kingae survival in the bloodstream,
indicating that at least some of the exopolysaccharide is anchored to the bacterial surface. Preliminary results
indicate that pooled serum from healthy adults and convalescent serum samples from children with invasive K.
kingae disease contain antibodies against the exopolysaccharide. In this proposal, we will elucidate the
mechanism by which the type 1 and type 2 exopolysaccharides are synthesized and anchored to the bacterial
surface. In addition, we will elucidate the pathogenic properties of the type 1 and type 2 exopolysaccharides.
We will also elucidate the immunogenicity and protective efficacy of the exopolysaccharides. The proposed
studies will provide fundamental insight into K. kingae pathogenicity and basic aspects of bacterial
exopolysaccharides. These studies will also facilitate development of a K. kingae vaccine and antibody-based
therapeutics against other pathogens with galactofuranose-containing surface structures.

## Key facts

- **NIH application ID:** 10734775
- **Project number:** 5R01AI172841-02
- **Recipient organization:** CHILDREN'S HOSP OF PHILADELPHIA
- **Principal Investigator:** Joseph W. St. Geme
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $445,000
- **Award type:** 5
- **Project period:** 2022-11-04 → 2027-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10734775

## Citation

> US National Institutes of Health, RePORTER application 10734775, Pathogenicity of the emerging pathogen Kingella kingae (5R01AI172841-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10734775. Licensed CC0.

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