Pathogenicity of the emerging pathogen Kingella kingae

新出现的病原体金氏菌的致病性

基本信息

  • 批准号:
    10559927
  • 负责人:
  • 金额:
    $ 44.5万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-11-04 至 2027-10-31
  • 项目状态:
    未结题

项目摘要

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.
金氏菌是一种侵入性革兰氏阴性病原体,最近被认为是主要病因

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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Joseph W. St. Geme其他文献

The effect of age on the synthesis of herpes simplex virus by rabbit skin in vitro
  • DOI:
    10.1016/s0022-3476(66)80533-4
  • 发表时间:
    1966-11-01
  • 期刊:
  • 影响因子:
  • 作者:
    Joseph W. St. Geme;Josephine M. Brumbaugh
  • 通讯作者:
    Josephine M. Brumbaugh
A search for the reservoir of cytomegalovirus in salivary gland tissue
  • DOI:
    10.1016/s0022-3476(68)80337-3
  • 发表时间:
    1968-04-01
  • 期刊:
  • 影响因子:
  • 作者:
    Robert W. ten Bensel;Joseph W. St. Geme
  • 通讯作者:
    Joseph W. St. Geme
Culture-negative endocarditis caused by Bartonella henselae.
由汉赛巴尔通体引起的培养阴性心内膜炎。
  • DOI:
  • 发表时间:
    1998
  • 期刊:
  • 影响因子:
    3.3
  • 作者:
    Elizabeth Baorto;R.Mark Payne;Leonard N. Slater;Fred Lopez;D. Relman;Kyung;Joseph W. St. Geme
  • 通讯作者:
    Joseph W. St. Geme
Failure to detect subtle neurotropism of live, attenuated measles virus vaccine
  • DOI:
    10.1016/s0022-3476(67)80163-x
  • 发表时间:
    1967-01-01
  • 期刊:
  • 影响因子:
  • 作者:
    Joseph W. St. Geme;Francis S. Wright;Frank Jones;Franz Halberg;John A. Anderson
  • 通讯作者:
    John A. Anderson
Some immunologic and virologic aspects of apparent intrauterine mumps virus infection and subsequent primary endocardial fibroelastosis
  • DOI:
    10.1016/s0022-3476(64)80138-4
  • 发表时间:
    1964-12-01
  • 期刊:
  • 影响因子:
  • 作者:
    Joseph W. St. Geme;George R. Noren;Paul Adams
  • 通讯作者:
    Paul Adams

Joseph W. St. Geme的其他文献

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{{ truncateString('Joseph W. St. Geme', 18)}}的其他基金

Molecular basis of virulence in the emerging pathogen Kingella kingae
新发病原体 Kingella kingae 毒力的分子基础
  • 批准号:
    8731463
  • 财政年份:
    2013
  • 资助金额:
    $ 44.5万
  • 项目类别:
Biology of the HMW1 and HMW2 Adhesins of H. Influenzae
流感嗜血杆菌 HMW1 和 HMW2 粘附素的生物学
  • 批准号:
    7850275
  • 财政年份:
    2009
  • 资助金额:
    $ 44.5万
  • 项目类别:
Center for Molecular & Cellular Studies of Ped Disease
分子中心
  • 批准号:
    7994221
  • 财政年份:
    2003
  • 资助金额:
    $ 44.5万
  • 项目类别:
Center for Molecular & Cellular Studies of Ped Disease
分子中心
  • 批准号:
    8197163
  • 财政年份:
    2003
  • 资助金额:
    $ 44.5万
  • 项目类别:
Haemophilus Hap-mediated Microcolony Formation
嗜血杆菌 Hap 介导的微菌落形成
  • 批准号:
    7157620
  • 财政年份:
    2003
  • 资助金额:
    $ 44.5万
  • 项目类别:
Center for Molecular & Cellular Studies of Ped Disease
分子中心
  • 批准号:
    7001196
  • 财政年份:
    2003
  • 资助金额:
    $ 44.5万
  • 项目类别:
Center for Molecular & Cellular Studies of Ped Disease
分子中心
  • 批准号:
    7385470
  • 财政年份:
    2003
  • 资助金额:
    $ 44.5万
  • 项目类别:
Center for Molecular & Cellular Studies of Ped Disease
分子中心
  • 批准号:
    7166800
  • 财政年份:
    2003
  • 资助金额:
    $ 44.5万
  • 项目类别:
CHOP Pediatric Scholars Program
CHOP 儿科学者计划
  • 批准号:
    8498900
  • 财政年份:
    2003
  • 资助金额:
    $ 44.5万
  • 项目类别:
CHOP Pediatric Scholars Program
CHOP 儿科学者计划
  • 批准号:
    10061633
  • 财政年份:
    2003
  • 资助金额:
    $ 44.5万
  • 项目类别:

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