Burkholderia sp: Identification of major clonal lineages

描述：（由申请人提供）：伯克氏菌属中的某些细菌物种能够引起严重的人类感染。mallei B.和pseudomallei B.分别是腺体病和类鼻疽病的病原体，近年来作为生物恐怖主义的病原体引起了人们的关注。洋葱芽孢杆菌复合体（Bcc）中的物种是新出现的医院病原体，能够在患有慢性肉芽肿病（CGD）或囊性纤维化（CF）的人中引起危及生命的感染，这是高加索人中最常见的遗传性致死疾病。在CF中，Bcc引起的呼吸道感染通常对抗菌药物治疗难以治愈，很大一部分患者死于迅速进行性肺恶化和败血症。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，已发现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物进行基因分型，确定人类致病的Bcc的主要克隆谱系，以及（ii）通过减法杂交方法确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。基因分型数据也是寻求菌株类型与Bcc感染临床过程相关的未来结果研究的先决条件。鉴定主要克隆的特异性基因将为研究这些基因在伯克氏菌中作为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表征这些毒力决定因素在人感染中增强Bcc致病性和/或传播性的机制。这将有助于开发预防和治疗Bcc感染的新策略，并将为涉及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为密切相关的B. mallei和B. pseudomallei的毒力机制和人际传播机制提供及时的信息。

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.