Burkholderia sp: Identification of major clonal lineages

伯克霍尔德氏菌：主要克隆谱系的鉴定

• 批准号: 6596573
• 负责人: JOHN J LIPUMA
• 金额: $ 7.63万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-04-01 至 2005-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6596573
• 关键词: Burkholderia; bacteria infection mechanism; bacterial genetics; bioterrorism /chemical warfare; clone cells; communicable disease transmission; computer assisted sequence analysis; computer program /software; genetic strain; genotype; polymerase chain reaction; subtraction hybridization; virulence

DESCRIPTION: (provided by applicant): Certain bacterial species within the genus Burkholderia are capable of causing significant human infection. B. mallei and B. pseudomallei, the causative agents of glanders and melioidosis, respectively, have gained attention recently as agents of bioterrorism. Species within the B. cepacia complex (Bcc) are emerging nosocomial pathogens and are capable of causing life-threatening infection in persons with chronic granulomatous disease (CGD) or cystic fibrosis (CF), the most common inherited lethal disorder in Caucasians. In CF, respiratory tract infection by Bcc is generally refractory to antimicrobial therapy and a significant proportion of patients succumbs to rapidly progressive pulmonary deterioration and sepsis. Recent work indicates that some Bcc species are much more frequently involved in infection in CF than others. Furthermore, at a subspecies level, certain strains or clones have been identified that infect multiple CF patients, suggesting that they have an enhanced ability to infect or to be transmitted within this population. The goals of the proposed research are to (i) identify major clonal lineages of human disease-causing Bcc by genotyping an extensive collection of isolates recovered from CF sputum culture, and (ii) identify genes specific to these major clones by using subtractive hybridization methodology. In the short term, the genotyping analysis will have an immediate impact on efforts to optimize current infection control strategies in CF. The genotyping data are also a prerequisite to future outcomes studies that will seek to correlate strain type and clinical course of Bcc infection. The identification of genes specific to major clones will provide an immediate avenue to investigate the potential roles of these genes as virulence determinants in Burkholderia. The long-term objectives of this work are to characterize the mechanisms whereby these virulence determinants enhance the pathogenicity and/or transmissibility of Bcc in human infection. This will enable the development of novel strategies to prevent and treat Bcc infections, and will also provide valuable insights to mechanisms involved in transmission of other respiratory pathogens. A better understanding of the pathogenicity of Bcc species is also likely to provide timely information regarding the mechanisms of virulence and person-to-person transmission of the closely related species B. mallei and B. pseudomallei.

描述：（由申请人提供）：伯克霍尔德杆菌属内的某些细菌物种能够引起严重的人类感染。 鼻疽和类鼻疽分别是鼻疽和类鼻疽的病原体，最近作为生物恐怖主义的媒介而受到关注。 洋葱伯克霍尔德杆菌复合体 (Bcc) 内的物种是新出现的医院病原体，能够对患有慢性肉芽肿病 (CGD) 或囊性纤维化 (CF) 的患者造成危及生命的感染，囊性纤维化是白种人中最常见的遗传性致命性疾病。在 CF 中，Bcc 引起的呼吸道感染通常对抗菌药物治疗无效，并且相当一部分患者死于快速进展的肺部恶化和脓毒症。 最近的研究表明，一些 Bcc 物种比其他物种更频繁地参与 CF 感染。此外，在亚种水平上，已鉴定出某些菌株或克隆可感染多个 CF 患者，这表明它们在该人群中感染或传播的能力增强。 拟议研究的目标是（i）通过对从 CF 痰培养中回收的大量分离株进行基因分型来鉴定人类致病 Bcc 的主要克隆谱系，以及（ii）通过使用消减杂交方法鉴定这些主要克隆的特异性基因。 在短期内，基因分型分析将对优化当前 CF 感染控制策略的努力产生直接影响。 基因分型数据也是未来结果研究的先决条件，未来研究将寻求将 Bcc 感染的菌株类型和临床病程关联起来。 主要克隆特异基因的鉴定将为研究这些基因作为伯克霍尔德氏菌毒力决定因素的潜在作用提供直接途径。 这项工作的长期目标是确定这些毒力决定因素增强 Bcc 在人类感染中的致病性和/或传播性的机制。 这将使开发预防和治疗 Bcc 感染的新策略成为可能，并且还将为其他呼吸道病原体传播的机制提供有价值的见解。 更好地了解 Bcc 物种的致病性也可能及时提供有关密切相关物种鼻疽杆菌和拟鼻疽杆菌的毒力和人际传播机制的信息。