| 论文题目: | Comparative genomic analysis of Mycobacterium tuberculosis clinical isolates |
|---|---|
| 作者: | Liu Fei#, Hu Yongfei#, Wang Qi#, Li Hong, Min, George F Gao, Liu Cui Hua*, Zhu Baoli |
| 联系作者: | Liu Cui Hua* |
| 刊物名称: | BMC Genomics |
| 期: | 15 |
| 卷: | |
| 页: | 469 |
| 年份: | 2014 |
| 影响因子: | 4.615 |
| 论文下载: | 下载地址 |
| 摘要: | BACKGROUND: Due to excessive antibiotic use, drug-resistant Mycobacterium tuberculosis has become a serious public health threat and a major obstacle to disease control in many countries. To better understand the evolution of drug-resistant M. tuberculosis strains, we performed whole genome sequencing for 7 M. tuberculosis clinical isolates with different antibiotic resistance profiles and conducted comparative genomic analysis of gene variations among them. RESULTS: We observed that all 7 M. tuberculosis clinical isolates with different levels of drug resistance harbored similar numbers of SNPs, ranging from 1409-1464. The numbers of insertion/deletions (Indels) identified in the 7 isolates were also similar, ranging from 56 to 101. A total of 39 types of mutations were identified in drug resistance-associated loci, including 14 previously reported ones and 25 newly identified ones. Sixteen of the identified large Indels spanned PE-PPE-PGRS genes, which represents a major source of antigenic variability. Aside from SNPs and Indels, a CRISPR locus with varied spacers was observed in all 7 clinical isolates, suggesting that they might play an important role in plasticity of the M. tuberculosis genome. The nucleotide diversity (capital EL, Cyrillic value) and selection intensity (dN/dS value) of the whole genome sequences of the 7 isolates were similar. The dN/dS values were less than 1 for all 7 isolates (range from 0.608885 to 0.637365), supporting the notion that M. tuberculosis genomes undergo purifying selection. The capital EL, Cyrillic values and dN/dS values were comparable between drug-susceptible and drug-resistant strains. CONCLUSIONS: In this study, we show that clinical M. tuberculosis isolates exhibit distinct variations in terms of the distribution of SNP, Indels, CRISPR-cas locus, as well as the nucleotide diversity and selection intensity, but there are no generalizable differences between drug-susceptible and drug-resistant isolates on the genomic scale. Our study provides evidence strengthening the notion that the evolution of drug resistance among clinical M. tuberculosis isolates is clearly a complex and diversified process. |
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