Comparative genomic analysis of Mycobacterium tuberculosis Beijing- like strains revealed specific genetic variations associated with virulence and drug resistance

被引:23
作者
Rodriguez-Castillo, Juan German [1 ]
Pino, Camilo [2 ]
Fernando Nino, Luis [2 ]
Carlos Rozo, Juan [3 ]
Llerena-Polo, Claudia [4 ]
Parra-Lopez, Carlos A. [1 ]
Tauch, Andreas [5 ]
Murcia-Aranguren, Martha Isabel [1 ]
机构
[1] Univ Nacl Colombia, Dept Microbiol, Grp MICOBACUN, Fac Med, Bogota 111321, Colombia
[2] Univ Nacl Colombia, Fac Ingn, Grp BioLISI, Bogota 111321, Colombia
[3] Ctr Int Entrenamiento & Invest Med CIDEIM, Cali 760031, Colombia
[4] Inst Nacl Salud, Bogota 111321, Colombia
[5] Univ Bielefeld, Ctr Biotechnol CeBiTec, D-33615 Bielefeld, Germany
关键词
Mycobacterium tuberculosis; Beijing-like; Comparative genomics; Virulence; Multidrug resistant; INDUCTION; GENOTYPE; MUTATION; COMPLEX; SPREAD; FAMILY; MICROEVOLUTION; BUENAVENTURA; TRANSMISSION; COEVOLUTION;
D O I
10.1016/j.meegid.2017.07.022
中图分类号
R51 [传染病];
学科分类号
100401 ;
摘要
Isolates of the Mycobacterium tuberculosis lineage 2/East-Asian are considered one of the most successful strains due to their increased pathogenicity, hyper-virulence associated with drug resistance, and high transmission. Recent studies in Colombia have shown that the Beijing-like genotype is associated with multidrug-resistance and high prevalence in the southwest of the country, but the genetic basis of its success in dissemination is unknown. In contribution to this matter, we obtained the whole sequences of six genomes of clinical isolates assigned to the Beijing-like genotype. The genomes were compared with the reference genome of M. tuberculosis H37Rv and 53 previously published M. tuberculosis genomes. We found that the six Beijing-like isolates belong to a modern Beijing sub-lineage and share specific genomic variants: i. e. deletion in the PPE8 gene, in Rv3806c (ubiA) responsible of high ethambutol resistance and in Rv3862c (whiB6) which is involved in granuloma formation and virulence, are some of them. Moreover, each isolated has exclusively single nucleotide polymorphisms (SNPs) in genes related with cell wall processes and cell metabolism. We identified polymorphisms in genes related to drug resistance that could explain the drug-resistant phenotypes found in the six isolates from Colombia. We hypothesize that changes due to these genetic variations contribute to the success of these strains. Finally, we analyzed the IS6110 insertion sequences finding very low variance between them, suggesting that SNPs is the major cause of variability found in Beijing-like strains circulating in Colombia.
引用
收藏
页码:314 / 323
页数:10
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