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）：Burkholderia属内的某些细菌物种能够引起重大的人类感染。 B. Mallei和B. pseudomallei（分别是腺体和黑胶病的病因，分别是生物恐怖主义的药物，分别引起了人们的关注。 西肝杆菌复合物（BCC）中的物种是新兴的医院病原体，能够引起慢性肉芽肿性疾病（CGD）或囊性纤维化（CF）的人的威胁生命的感染，这是高加索人中最常见的遗传性致命疾病。在CF中，BCC呼吸道感染通常是对抗菌治疗的难治性，并且很大一部分患者屈服于快速进行性肺部恶化和败血症。 最近的工作表明，某些BCC物种在CF中的感染频繁比其他BCC感染更频繁。此外，在亚种上，已经确定了某些菌株或克隆感染了多个CF患者，这表明它们具有增强的感染能力或在该人群中传播的能力。 拟议的研究的目标是（i）通过基因分型从CF痰培养中恢复的广泛分离株来确定引起人类病BCC的主要克隆谱系，以及（ii）通过使用减去性杂交方法来识别这些主要克隆特有的基因。 在短期内，基因分析分析将对优化CF中当前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，该研究将寻求将BCC感染的应变类型和临床过程相关联。 特定于主要克隆的基因的鉴定将提供直接的途径，以研究这些基因作为Burkholderia中毒力决定因素的潜在作用。 这项工作的长期目标是表征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。 这将使新的策略发展为预防和治疗BCC感染，并将为参与其他呼吸道病原体传播的机制提供宝贵的见解。 对BCC物种的致病性有更好的理解也可能会及时提供有关毒力机制以及密切相关物种的人对人向人的传播的信息。