多耐药Myroides odoratimimus PR63039的全基因组测序和生物信息学分析

发布时间：2018-04-30 04:37

本文选题：Myroides + odoratimimus　；参考：《华侨大学》2017年硕士论文

【摘要】：Myroides sp.菌,原名芳香黄杆菌(Flavobacterium odoratum),是非发酵性、专性需氧型、革兰氏阴性不动杆菌,在代谢过程中能产生具有水果香味的黄色物质。Myroides sp.能感染免疫力低下的人群,造成各种院内感染甚至爆发感染,如:泌尿系统感染、蜂窝组织炎、菌血症、恶性肿瘤、坏死性筋膜炎、败血症、心室炎和糖尿病并发症等。Myroides sp.感染难治愈,因为Myroides sp.菌耐药性广泛,且抗生素耐药机制尚不清楚。本论文对一株临床分离的多耐药Myroides odoratimimus(M.odoratimimus)菌PR63039,采用PacBio RSII测序系统,对其进行全基因组测序和生物信息学分析,试图在基因组水平阐明M.odoratimimus PR63039的抗生素耐药和致病机制、并比较临床M.odoratimimus分离菌株基因组之间的异同。M.odoratimimus PR63039基因组由染色体(4,366,950 bp)和质粒(90,798bp)组成。使用CG viewer,我们获得PR63039的基因组圈图。PR63039基因组含有大量的耐药基因,包括:β-内酰胺耐药基因、四环素耐药基因、氯霉素耐药基因、喹诺酮耐药基因、多耐药质子泵基因、耐药突变基因Staphylococcus aureus rpoB和Pseudomonas aeruginosa gyrA。该菌耐药基因的分布是独特的,我们发现了一个耐药区域,并将其命名为MY63039-RR。通过分析可知,菌株PR63039抗生素耐药基因与药敏试验(AST)中的耐药谱表型基本一致。对M.odoratimimus PR63039的基因组分析部分澄清了其抗生素多耐药机制。此外,M.odoratimimus PR63039基因组中还预测到38个毒力因子和两个原噬菌体。四株临床M.odoratimimus菌株(M.odoratimimus PR63039、M.odoratimimus CCUG10230、M.odoratimimus CCUG12901、M.odoratimimus CIP101113)之间的比较基因组学分析结果表明,它们的基因组同源性比较大。系统发育树显示菌株CCUG10230、CCUG12901和CIP101113可能属于相同的克隆。所有菌株基因组中均存在多种抗生素耐药基因,CCUG12901、CIP101113和CCUG10230中预测到的耐药基因几乎一致。共线性分析表明四个基因组是非常相似的,即使存在一些染色体重排。通过CRISPR预测分析,我们发现菌株PR63039含有三种类型的CRISPR,CCUG10230含有四种类型的CRISPR,但菌株CCUG12901和CIP101113的基因组中无CRISPR序列。此外,所有四株临床分离菌基因组中均预测到原噬菌体序列,尽管原噬菌体组成元件略有差别。总体上,该论文在基因组水平上部分阐明了M.odoratimimus PR63039抗生素多耐药机制、致病力机制、4株临床M.odoratimimus致病菌之间的同源性。这些基因组数据和发现为临床M.odoratimimus菌感染的治疗和新抗生素研发提供了理论指导。
[Abstract]:Myroides sp. Flavobacterium odoratumum, which is non-fermentative, specific aerobic, Gram-negative Acinetobacter sp. can produce the yellow substance. Myroides sp. in the metabolic process. It can infect people with low immunity, causing various nosocomial infections and even erupting infections, such as urinary tract infection, cellulitis, bacteremia, malignant tumor, necrotizing fasciitis, septicemia, ventricular inflammation and diabetic complications, etc. Myroides spp. Infection is difficult to cure because of Myroides sp. Antibiotic resistance is widespread and the mechanism of antibiotic resistance is unclear. In this paper, a clinical isolates of multidrug resistant Myroides odoratimim M. odoratimimia PR63039 were sequenced by PacBio RSII sequencing system. The whole genome of PR63039strain was sequenced and bioinformatics analysis was carried out to elucidate the mechanism of antibiotic resistance and pathogenesis of M.odoratimimus PR63039 at the genomic level. The genome of M. odoratimimus was composed of chromosome 4366950bpand plasmid 90798bp. Using CG viewer, we obtained that the genome of PR63039, PR63039, contained a large number of drug-resistant genes, including 尾 -lactam resistance, tetracycline resistance, chloramphenicol resistance, quinolone resistance, and multidrug resistance proton pump genes. Staphylococcus aureus rpoB and Pseudomonas aeruginosa gyrA. The distribution of drug resistance gene was unique. We found a drug resistance region and named it MY63039-RR. The results showed that the antibiotic resistance genes of the strain PR63039 were basically consistent with the drug resistance patterns in the drug sensitivity test (AST). The genome analysis of M.odoratimimus PR63039 clarifies the mechanism of multidrug resistance of M.odoratimimus. In addition, 38 virulence factors and two prophages were predicted in the genome of M. odoratimimus PR63039. The comparative genomics analysis between four clinical M.odoratimimus strains M. odoratimimus PR63039 and M. odoratimimus CCUG10230 (M.odoratimimus CCUG12901, M.odoratimimus CIP101113) showed that their genomes were homologous. Phylogenetic tree showed that CCUG10230 CCUG12901 and CIP101113 might belong to the same clone. All strains had multiple antibiotic resistance genes CCUG12901CIP101113 and the predicted resistance genes in CCUG10230 were almost the same. Co-linear analysis showed that the four genomes were very similar, even if there were some chromosome rearrangements. By CRISPR prediction analysis, we found that the strain PR63039 contained three types of CRISPRA CCUG10230, but no CRISPR sequence in the genome of CCUG12901 and CIP101113. In addition, prophage sequences were predicted in the genomes of all four clinical isolates, although the composition of the phage was slightly different. In general, at the genomic level, the mechanism of multidrug resistance of M.odoratimimus PR63039 and the homology of four clinical M.odoratimimus pathogens were elucidated in this paper. These genomic data and findings provide theoretical guidance for the treatment of clinical M.odoratimimus infection and the development of new antibiotics.
【学位授予单位】：华侨大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R378

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