Genes associated with epidemic Burkholderia cenocepacia

与流行性新洋葱伯克霍尔德杆菌相关的基因

• 批准号: 7384875
• 负责人: JOHN J LIPUMA
• 金额: $ 24.03万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-12-04 至 2009-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7384875
• 关键词: Age; Antibiotics; Bacteria; Bacterial Genes; Bacteriophages; Burkholderia; Burkholderia cepacia complex; Caucasians; Caucasoid Race; Cause of Death; Chronic; Classification; Clinical; Collection; Complement; Cystic Fibrosis; DNA; DNA Insertion Elements; Development; Disease; Disease regression; Elements; Employee Strikes; Epidemic; Foundations; Frequencies; Gene Cluster; Gene Expression; Gene Pool; Genes; Genomics; Guanine + Cytosine Composition; Human; Infection; Inflammation; Inherited; Intercistronic Region; Life; Location; Lung Transplantation; Lung diseases; Microarray Analysis; Morbidity - disease rate; North America; Numbers; Open Reading Frames; Operative Surgical Procedures; Operon; Outcome; Patients; Persons; Phylogenetic Analysis; Policies; Population; Rate; Relative (related person); Research; Resistance; Respiratory Failure; Respiratory Tract Infections; Series; Staging; Testing; Trees; Virulence; Virulent; comparative; cystic fibrosis patients; gene function; genetic element; genome sequencing; innovation; interest; member; mortality; novel; transmission process; transposon/insertion element

DESCRIPTION (provided by applicant): Cystic fibrosis (CF) is the most common lethal inherited disease in Caucasians in North America. Among the bacterial species that cause the chronic respiratory tract infections that characterize CF are members of the Burkholderia cepacia complex (Bcc). Infection with Bcc is associated with significantly increased rates of morbidity and mortality in CF, and is generally considered an absolute contraindication to lung transplantation. Species within the Bcc are both phylogenetically very closely related and phenotypcially nearly indistinguishable. Despite this close relationship, however, Bcc species show a striking difference in the frequency with which they cause infection in CF, with B. cenocepacia being particularly common in this patient population. Furthermore, so-called epidemic B. cenocepacia strains infect a great many patients, and appear to have an enhanced capacity for inter-patient transmission and virulence. At present, the biologic underpinnings of these striking differences in disease frequency and virulence are unknown. We hypothesize that specific bacterial factors contribute to the disproportionate distribution and virulence of epidemic B. cenocepacia strains in CF. In this Exploratory/Developmental Project (R21), we will test this hypothesis by using a comparative genomics approach to identify genes that are specifically associated with epidemic B. cenocepacia. We will take advantage of our extensive strain collection, the large number of recently sequenced Burkholderia strains, innovative microarray technology, and 20 years of epidemiologic analysis of Bcc to identify these genetic elements. Project Narrative--Bacteria within the Burkholderia cepacia complex cause severe, life threatening respiratory infection in persons with cystic fibrosis (CF). These bacteria are typically resistant to most available antibiotics, making effective treatment of infection impossible. Furthermore, infection may spread between patients, and this has resulted in strict policies to separate CF patients from each other. Certain specific strains are more commonly found to cause infection and are associated with worse disease. The primary aim of this project is to discover the specific factors that allow these strains to spread and cause severe infection in persons with CF.

描述（由申请人提供）：囊性纤维化（CF）是北美白种人中最常见的致命遗传性疾病。引起 CF 特征的慢性呼吸道感染的细菌种类之一是洋葱伯克霍尔德菌复合体 (Bcc) 的成员。 Bcc 感染与 CF 发病率和死亡率显着增加相关，通常被认为是肺移植的绝对禁忌症。 Bcc 内的物种在系统发育上都非常密切相关，但在表型上几乎无法区分。然而，尽管存在这种密切的关系，Bcc 物种在引起 CF 感染的频率上表现出显着差异，其中新洋葱伯克霍尔德杆菌 (B. cenocepacia) 在该患者群体中特别常见。此外，所谓的流行性新洋葱伯克霍尔德杆菌菌株感染了大量患者，并且似乎具有增强的患者间传播能力和毒力。目前，疾病频率和毒力这些显着差异的生物学基础尚不清楚。我们假设特定的细菌因素导致 CF 中流行的新洋葱伯克霍尔德杆菌菌株的不成比例的分布和毒力。在这个探索/开发项目（R21）中，我们将通过使用比较基因组学方法来鉴定与流行性新洋葱伯克霍尔德氏菌特异性相关的基因来测试这一假设。我们将利用我们广泛的菌株收集、大量最近测序的伯克霍尔德杆菌菌株、创新的微阵列技术以及 20 年的 Bcc 流行病学分析来识别这些遗传元件。项目叙述——洋葱伯克霍尔德杆菌复合体中的细菌会导致囊性纤维化 (CF) 患者严重、危及生命的呼吸道感染。这些细菌通常对大多数可用的抗生素具有耐药性，因此无法有效治疗感染。此外，感染可能在患者之间传播，这导致了将 CF 患者相互隔离的严格政策。某些特定菌株更常见地引起感染并与更严重的疾病相关。该项目的主要目的是发现导致这些菌株传播并导致 CF 患者严重感染的具体因素。