Genes associated with epidemic Burkholderia cenocepacia

描述（由申请人提供）：囊性纤维化（CF）是北美白人中最常见的致死性遗传性疾病。在引起慢性呼吸道感染的细菌物种中，CF的特征是洋葱伯克霍尔德氏菌复合体（Bcc）的成员。Bcc感染与CF的发病率和死亡率显著增加相关，通常被认为是肺移植的绝对禁忌症。BCC内的物种在遗传学上非常接近，并且在表型上几乎无法区分。然而，尽管这种密切的关系，Bcc物种在CF中引起感染的频率上显示出显著的差异，其中B。新洋葱皮病在该患者群体中特别常见。此外，所谓的流行病B。新洋葱球菌菌株感染很多患者，并且似乎具有增强的患者间传播能力和毒力。目前，这些疾病频率和毒性的显著差异的生物学基础尚不清楚。我们推测，特定的细菌因素有助于不成比例的分布和流行性B的毒力。新洋葱菌株在CF.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鉴定与流行性B特异性相关的基因来验证这一假设。cenocepacia。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菌菌株，创新的微阵列技术，以及20年的Bcc流行病学分析来确定这些遗传因素。项目叙述--洋葱伯克霍尔德菌复合体中的细菌在囊性纤维化（CF）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耐药性，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，这导致了严格的政策，以将CF患者彼此分开。某些特定的菌株更常被发现引起感染，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导致CF患者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.