Genes associated with epidemic Burkholderia cenocepacia

描述(申请人提供)：囊性纤维化(CF)是北美高加索人最常见的致死性遗传病。在以洋葱伯克霍尔德菌复合体(BCC)为特征的慢性呼吸道感染的细菌种类中，洋葱伯克霍尔德菌复合体(BCC)是其特征。BCC感染与CF的发病率和死亡率显著增加有关，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非常接近，而在表型上几乎无法区分。然而，尽管有这种密切的关系，基底细胞癌物种在引起CF感染的频率上显示出显著的差异，在这一患者群体中，棘球绦虫感染尤其常见。此外，所谓的流行性猪瘟杆菌菌株感染了大量患者，并似乎具有增强的患者间传播和毒力能力。目前，这些疾病频率和毒力的显著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流行性阴沟肠杆菌在CF中的不成比例的分布和毒力。在这个探索/发展项目(R21)中，我们将通过使用比较基因组学方法来验证这一假说，以确定与流行的猪瘟特别相关的基因。我们将利用我们广泛的菌株收集、最近测序的大量伯克霍尔德菌菌株、创新的微阵列技术以及20年来对BCC的流行病学分析来确定这些遗传因素。项目简介--洋葱伯克霍尔德氏菌复合体内的细菌会在囊性纤维症患者中引起严重的、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抗药性，使感染的有效治疗变得不可能。此外，感染可能在患者之间传播，这导致了将CF患者彼此分开的严格政策。某些特定的菌株更常被发现会引起感染，并与更严重的疾病有关。该项目的主要目的是发现允许这些菌株传播并在CF患者中造成严重感染的特定因素。

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.