# Virulence mechanisms in the emerging pathogen Kingella kingae

> **NIH NIH R01** · CHILDREN'S HOSP OF PHILADELPHIA · 2020 · $420,000

## Abstract

Kingella kingae is an invasive gram-negative pathogen that has been recognized recently as a leading
cause of septic arthritis and osteomyelitis in young children, accounting for up to 78% of cases in children <4
years old. Estimates indicate that over 15,000 cases of septic arthritis and osteomyelitis occur annually among
children in the US, with the peak incidence in the first 3 years of life. Complications of septic arthritis and
osteomyelitis 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. Based
on epidemiologic data, the pathogenesis of K. kingae disease is believed to begin with colonization of the
upper respiratory tract and to involve invasion of the bloodstream and spread to joints, bones, and sometimes
other sites. In recent work, we established that type IV pili are essential for K. kingae adherence to respiratory
epithelial cells, suggesting a critical role in colonization of the upper respiratory tract. Further analysis
demonstrated that full-level pilus-mediated adherence is dependent on a trimeric autotransporter protein called
Knh. Additional studies revealed that isolates of K. kingae produce a polysaccharide capsule that interferes
with Knh-mediated adherence when pili are absent. There are four different polysaccharide capsule types,
including three that account for all cases of invasive disease and one that is found only in carrier isolates.
Based on analysis of our prototype invasive isolate, encapsulation is essential for full virulence in an infant rat
model of invasive disease. In the present proposal we will elucidate the interrelationship between type IV pili,
the Knh protein, and the polysaccharide capsule as determinants of K. kingae adherence to respiratory
epithelial cells. In addition, we will examine the role of pili, Knh, and capsule in a rhesus macaque monkey
model of upper respiratory tract colonization. We will also elucidate the pathogenic and immunologic
properties of the four K. kingae polysaccharide capsule types. The proposed studies will yield an improved
understanding of the pathogenesis of disease due to an understudied pathogen that is being recognized
increasingly as an important source of morbidity in young children, will define the mechanism that underlies a
novel model of interaction between an encapsulated pathogen and host cells, and will define the pathogenic
and immunologic properties of newly discovered polysaccharide capsules with unusual structures.

## Key facts

- **NIH application ID:** 9947855
- **Project number:** 5R01AI121015-05
- **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:** 2020
- **Award amount:** $420,000
- **Award type:** 5
- **Project period:** 2016-06-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9947855

## Citation

> US National Institutes of Health, RePORTER application 9947855, Virulence mechanisms in the emerging pathogen Kingella kingae (5R01AI121015-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9947855. Licensed CC0.

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