原发性皮肤诺卡菌病中致病菌株的泛基因组学研究

The primary cutaneous nocardiosis is an infectious condition that usually involves in immunocompetent individuals with huge medical burden. The disease remains a diagnostic and therapeutic challenge to the clinicians. A few evidences reveal that Nocardia species have a rapid gene evolution and can acquire different functional genes including virulence gene by the horizontal transfer of abundance genomic components from environmental micro-organisms. The project tends to investigate the pan-genome of the Nocardia species causing primary cutaneous infections by whole genomes sequencing. With morphologic, physicochemical investigations and mass spectrometry, the diversities among strains are described. The whole gene map of pathogenic nocardia species are constructed by the next-generation sequencing. Based on bioinformatics method, pan-genome research strategies and the GenBank database, the genome features of pathogenic Nocardia are revealed and the core genome and specific genome are well defined. This subject is aimed to solve the following scientific problems: 1) The genomic characteristics and evolution of pathogenic Nocardia species; 2) Screening significant virulence genes and special secondary metabolites of Nocardia strains; 3) Are the Nocardia species becoming an emerging human pathogen.

原发性皮肤诺卡菌病是一种常累及免疫功能正常人群的感染性疾病，医疗负担重，诊治具有挑战性。研究表明诺卡菌基因进化迅速，可通过基因水平转移与周围环境进行大量遗传物质交换，从而获得不同的功能基因，包括毒力基因。本项目拟通过致病性诺卡菌的分离及全基因组序列分析，致力于原发性皮肤诺卡菌病致病菌株的泛基因组研究。通过形态学，理化性质研究及质谱指纹图谱技术分析菌株间的差异；利用高通量测序构建致病菌株的全基因组完成图；依据生物信息学方法和泛基因组学研究思路，整合GenBank数据库信息，明确致病性诺卡菌基因组特点,界定其核心基因组与特异性基因组。本课题拟解决以下科学问题：1）揭示致病性诺卡菌基因组特点及其进化过程；2）筛选致病性诺卡菌重要毒力基因和特殊次级代谢产物；3）明确诺卡菌是否已经成为一种新型的人类致病菌。

原发性皮肤诺卡菌病是一种全球散发的疾病, 常累及免疫功能正常人群, 诊断极具挑战性，医疗负担重,且其致病菌种复杂多样。本课题通过对原发性皮肤诺卡菌病的诊治，收集了大量的致病菌株，我们针对致病性诺卡菌生理生化特性、菌种鉴定及其基因组特点进行研究。明确了致病性诺卡菌的生物性状特点，同时发现诺卡菌临床分离株菌种构成丰富，传统16SrDNA测序不能够完全将诺卡菌鉴定至种水平，而基于全基因组测序的单核苷酸同源性分析和DNA杂交能更加精准的对该菌属进行种水平鉴定，并由此发现一种新的诺卡菌——华西诺卡菌。最后我们对不同来源的诺卡菌基因组进行分析，筛选出诺卡菌核心基因组和非核心基因组，为下一步研究诺卡菌致病的分子机制提供了遗传学基础，具有一定参考意义。