Comparative genomic analysis of Mycobacterium tuberculosis clinical isolates
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 ((JI) 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 (JI)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.
Mycobacterium tuberculosis Drug resistance Single nucleotide polymorphisms Whole genome sequencing Evolution
Fei Liu Yongfei Hu Qi Wang Hong Min Li George F Gao Cui Hua Liu Baoli Zhu
CAS key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Aca Institute for Tuberculosis Research, the 309th Hospital, Beijing, China
国际会议
北京
英文
379-391
2018-03-29（万方平台首次上网日期，不代表论文的发表时间）