Novel genes involved in survival in vivo in the environmental pathogen Burkholderia cenocepacia

环境病原体被定义为通常在人类宿主之外度过其生命周期的微生物，但当被引入人类时，会以可测量的频率引起疾病。其中一些只影响免疫功能低下的患者或有基础疾病的人。洋葱伯克霍尔德菌复合体是一组环境细菌，具有在不同环境中生存和降解某些污染物的非凡能力。不幸的是，洋葱芽胞杆菌复合体已经成为患有遗传性囊性纤维化（CF）的儿童和年轻人的主要健康风险。CF是加拿大年轻人最常见、最致命的遗传性疾病，主要影响肺部和消化系统。洋葱芽孢杆菌复合体感染这些患者，其存在与肺功能恶化有关，最终可导致死亡。洋葱芽孢杆菌复合体被发现在人体肺部定植并持续存在的一些方式，可能与它们在土壤和其他不断变化的环境中生存的能力有关。有可能，一些赋予优势的基因使细菌在不同条件下茁壮成长，也对这些细菌作为病原体的生存有作用。该项目将研究体外生存所需的某些代谢和基本功能是否与体内生存相关。为了这个目的，秀丽隐杆线虫，一种在土壤中常见的蠕虫将被用作感染模型。这种蠕虫是遗传学研究的理想模型，因为它很容易操纵特定的基因，而且与其他动物模型相比，这种蠕虫可以大量快速生长，甚至可以冷冻起来供以后使用。秀丽隐杆线虫生活在土壤中，因此它不断与细菌和其他微生物接触，并且具有高度发达的系统，不仅可以识别细菌，还可以对细菌做出反应。它的先天免疫系统对特定细菌做出适当反应的能力与哺乳动物非常相似，所以从长远来看，这个系统将帮助我们了解洋葱芽孢杆菌是如何克服肺部的免疫反应并导致感染的。

Environmental pathogens are defined as microorganisms that normally spend their lifecycle outside the human host but when introduced to humans cause disease with measurable frequency. Some of them affect only immunocompromised patients or people with underlying diseases. Burkholderia cepacia complex are a group of environmental bacteria with an extraordinary capacity to survive in diverse environments and also to degrade certain pollutants. Unfortunately B. cepacia complex has become a major health risk for children and young adults with the genetic disease cystic fibrosis (CF). CF is the most common, fatal genetic disease in young Canadians affecting mainly the lungs and the digestive system. B. cepacia complex infect these patients and its presence is associated with a deterioration of the lung function that ultimately can cause death. Some of the ways B. cepacia complex has found to colonize and persist in the human lung may be related to their capacity to survive in the soil, and other ever-changing environments. It is possible that some of the genes that confer advantages allowing the bacteria to thrive in different conditions also have a function in the survival of these bacteria as pathogens. This project will investigate if certain metabolic and essential functions known to be required for survival in vitro are relevant for survival in vivo. For this purpose  C. elegans, a worm commonly found in the soil will be used as an infection model. The worm is an ideal model for genetic studies, because it is easy to manipulate specific genes, and in contrast to other animal models, large quantities of the worms can be grown quickly and can even be frozen and used later. C. elegans lives in the soil, so it continually comes into contact with bacteria and other microbes and has a highly developed system for not only recognizing bacteria, but also responding to them. The ability of its innate immune system to respond appropriately to specific bacteria is very similar to that of mammals so the system will help us to understand in the long term how B. cepacia overcome the immune response in the lungs and causes infection.