Microbial community ecology of chronic respiratory infections

慢性呼吸道感染的微生物群落生态学

• 批准号: NE/H019456/1
• 负责人: Christopher Van Der Gast
• 金额: $ 8.91万
• 依托单位: NERC CEH (Up to 30.11.2019)
• 依托单位国家: 英国
• 项目类别: Training Grant
• 财政年份: 2010
• 资助国家: 英国
• 起止时间: 2010 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=NE%2FH019456%2F1
• 关键词: Microbial; community; ecology; chronic; respiratory

The World Health Organisation has identified respiratory illness as one of the leading global causes of human morbidity and mortality. Set within an ecological framework, this CASE studentship will focus on the community ecology of microbial infections within the lungs of cystic fibrosis (CF) patients; where morbidity and mortality in CF patients is primarily caused by chronic microbial infections and concomitant airway inflammation. CF makes an ideal paradigm for chronic respiratory infections as it is a well defined disorder and typically has a more rapid decline in lung function (due to infection) than other respiratory illnesses. The microbiological analysis of clinical specimens has relied traditionally upon culture dependent methods prior to identification and research has focused upon only a few targeted bacterial pathogenic species including; Pseudomonas aeruginosa, Staphylococcus aureus, Haemophilus influenzae and Burkholderia cepacia complex (BCC). The use of molecular biological approaches, developed and widely used in environmental microbiology, promise to provide fresh insights into infections that have previously been considered well characterised. For example, recent molecular biological based studies have shown that the level of bacterial diversity in CF sputum was much higher than previously accepted. Although known pathogens clearly are important, it is only now being recognised that chronically colonized CF airways represent a surprisingly complex and diverse ecosystem and understanding the CF lung in terms of its community ecology could benefit our understanding of disease progression and influence treatment regimens. Here the PhD student will be provided with training in ecological modelling and statistics, molecular microbial ecology, clinical microbiology, and the latest cutting edge genomic sequencing techniques. This innovative inter-disciplinary training will allow the student to gain an entirely new level of understanding in CF microbiology and to address the following fundamental questions: (1) What are the diversity, abundance and distribution of bacterial taxa across clinically stable patients? (2) How do those community characteristics compare and contrast when patients suffer pulmonary exacerbations? (3) Are there regional differences in the bacterial community ecology for groups of CF patients attending different centres for CF excellence? (4) Do archaeal and eukaryotic organisms also have a role to play in disease in pulmonary exacerbations?

世界卫生组织已确定呼吸系统疾病是导致人类发病和死亡的主要全球原因之一。在生态框架内，这一案例研究将集中于囊性纤维化(CF)患者肺部微生物感染的社区生态；囊性纤维化患者的发病率和死亡率主要由慢性微生物感染和伴随的呼吸道炎症引起。Cf慢性呼吸道感染是一个理想的范例，因为它是一种定义明确的疾病，通常肺功能下降(由于感染)比其他呼吸道疾病更快。临床标本的微生物学分析在鉴定前传统上依赖于培养方法，研究仅集中在少数几个目标致病菌上，包括铜绿假单胞菌、金黄色葡萄球菌、流感嗜血杆菌和洋葱伯克霍尔德菌复合体(BCC)。在环境微生物学中开发和广泛使用的分子生物学方法的使用，有望为以前被认为具有良好特征的感染提供新的见解。例如，最近基于分子生物学的研究表明，CF痰中的细菌多样性水平比以前接受的要高得多。虽然已知的病原体显然很重要，但直到现在才认识到，长期定居的CF呼吸道代表着一个令人惊讶的复杂和多样化的生态系统，了解CF肺的群落生态有助于我们了解疾病的发展并影响治疗方案。在这里，博士生将接受生态建模和统计学、分子微生物生态学、临床微生物学和最新的尖端基因组测序技术方面的培训。这一创新的跨学科培训将使学生对CF微生物学有一个全新的理解，并解决以下基本问题：(1)临床稳定的患者中细菌分类群的多样性、丰度和分布是什么？(2)当患者发生肺部恶化时，这些群落特征是如何比较和对比的？(3)在不同的CF卓越中心就诊的CF患者群体的细菌群落生态是否存在地区差异？(4)古细菌和真核生物是否也在肺部加重的疾病中发挥作用？