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

Rodríguez-Castillo, Juan Germán; Pino, Camilo; Niño, Luís Fernando; Rozo, Juan Carlos; Llerena-Polo, Claudia; Parra-López, Carlos; Tauch, Andreas; Murcia-Aranguren, Martha Isabel

doi:10.1016/j.meegid.2017.07.022

Cited by 24 publications

(21 citation statements)

References 72 publications

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“…Except the frameshift deletion at the position 434226, all the remaining SNPs previously reported as exclusively present in the Beijing-like strains from Colombia (32) were also found in the MDR-TB Beijing strain 38765 that was subjected to WGS in this study (Table 2). Instead of the deletion at the position 434226, our Beijing MDR-TB strain (38765) also had a deletion just in the next nucleotide position (434227) (Table 3).…”

Section: Discussionsupporting

confidence: 57%

Genetic profiling ofMycobacterium tuberculosis“modern” Beijing strains from Southwest Colombia

Ramirez

Ferro

Díaz

et al. 2019

Preprint

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26Beijing strains of Mycobacterium tuberculosis (lineage2) have been associated 27 with drug-resistance and transmission of tuberculosis worldwide. Most of the Beijing 28 strains identified in the Colombian pacific coast exhibited a multidrug resistant (MDR) 29 phenotype, in contrast with the phenotype observed in Beijing isolates from other South-30 American countries. We wanted to evaluate the clonality and genetic background of the 31 Beijing strains isolated in Colombia that belong mostly to the spoligo-international type 32 (SIT) 190. Out of 37 Beijing stains characterized in an 8-years period, we identified five 33 Beijing clones; 36 that belong to the SIT190 type and only one to SIT1. Two loci in 34 VNTR typing: MIRU 39 and QUB11b exhibited the highest level of variation among 35 these strains. Out of the 37 Beijing strains, only one was drug susceptible, 28 36 represented MDR-TB, four extensively drug resistant TB (XDR-TB) and four pre-XDR-37 TB. The mutations rpoB S531L and katG S315T1 were the most common among the 38 MDR strains as reported elsewhere. Whole genome sequencing analysis allowed us to 39 classify them as modern lineage Beijing strains, sharing up to 76 out of the 275 SNPs 40 described in Beijing strains, as identified worldwide by Schürch et al; including 54 non-41 synonymous SNPs and 23 silent mutations. We were also able to confirm the presence 42 of 8 specific SNPs that were so far only found in the Beijing strains from Colombia. The 43 presence of modern Beijing strains, most of them representing MDR-TB, suggests a 44 different origin of this M. tuberculosis lineage compared to other Beijing strains found in 45 neighboring countries, such as Peru. The specific 8-SNP signature confirmed the 46 identity of these Colombian Beijing MDR strains. This work may serve as a genetic 3 47 baseline to study the evolution and spread of M. tuberculosis Beijing strains in 48 Colombia, which play an important role in the control of MDR-TB.

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Section: Discussionsupporting

confidence: 57%

Genetic profiling ofMycobacterium tuberculosis“modern” Beijing strains from Southwest Colombia

Ramirez

Ferro

Díaz

et al. 2019

Preprint

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“…M. tuberculosis Zt272 that resulted in increased bacterial load in lungs, decreased survival time and increased area of pneumonia relative to other strains in the intra-tracheally infected mice (Ribeiro et al, 2014 ). The M. tuberculosis Zaragoza strain caused outbreak in Zaragoza, Spain, and reached 18.7% of all isolates of M. tuberculosis in 2001 to 2004 (Jia et al, 2017 ; Rodríguez-Castillo et al, 2017 ). On the contrary, non-H112 clade strain included the streptomycin-dependent M. tuberculosis 18b strain, which has been reported to be severely attenuated in high-dose (>1,000 bacilli) aerosol infected mice model (Campos-Neto, 2016 ) although the virulence of other strains in this clade have not been phenotypically characterized.…”

Section: Resultsmentioning

confidence: 99%

“…WGS has emerged as a powerful tool to identify genetic determinants of mycobacterial virulence. Notably, comparative genomics approach has revealed possible associations between genetic polymorphisms and virulence diversity in M. tuberculosis (Jia et al, 2017 ; Rodríguez-Castillo et al, 2017 ). However, virulence of the M. tuberculosis strains used in most of these studies was largely unknown.…”

Section: Discussionmentioning

confidence: 99%

Comparative Whole-Genomic Analysis of an Ancient L2 Lineage Mycobacterium tuberculosis Reveals a Novel Phylogenetic Clade and Common Genetic Determinants of Hypervirulent Strains

Rajwani

Yam

Zhang

et al. 2018

Front. Cell. Infect. Microbiol.

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Background: Development of improved therapeutics against tuberculosis (TB) is hindered by an inadequate understanding of the relationship between disease severity and genetic diversity of its causative agent, Mycobacterium tuberculosis. We previously isolated a hypervirulent M. tuberculosis strain H112 from an HIV-negative patient with an aggressive disease progression from pulmonary TB to tuberculous meningitis—the most severe manifestation of tuberculosis. Human macrophage challenge experiment demonstrated that the strain H112 exhibited significantly better intracellular survivability and induced lower level of TNF-α than the reference virulent strain H37Rv and other 123 clinical isolates.Aim: The present study aimed to identify the potential genetic determinants of mycobacterial virulence that were common to strain H112 and hypervirulent M. tuberculosis strains of the same phylogenetic clade isolated in other global regions.Methods: A low-virulent M. tuberculosis strain H54 which belonged to the same phylogenetic lineage (L2) as strain H112 was selected from a collection of 115 clinical isolates. Both H112 and H54 were whole-genome-sequenced using PacBio sequencing technology. A comparative genomics approach was adopted to identify mutations present in strain H112 but absent in strain H54. Subsequently, an extensive phylogenetic analysis was conducted by including all publically available M. tuberculosis genomes. Single-nucleotide-polymorphisms (SNPs) and structural variations (SVs) common to hypervirulent strains in the global collection of genomes were considered as potential genetic determinants of hypervirulence.Results:Sequencing data revealed that both H112 and H54 were identified as members of the same sub-lineage L2.2.1. After excluding the lineage-related mutations shared between H112 and H54, we analyzed the phylogenetic relatedness of H112 with global collection of M. tuberculosis genomes (n = 4,338), and identified a novel phylogenetic clade in which four hypervirulent strains isolated from geographically diverse regions were clustered together. All hypervirulent strains in the clade shared 12 SNPs and 5 SVs with H112, including those affecting key virulence-associated loci, notably, a deleterious SNP (rv0178 p. D150E) within mce1 operon and an intergenic deletion (854259_ 854261delCC) in close-proximity to phoP.Conclusion: The present study identified common genetic factors in a novel phylogenetic clade of hypervirulent M. tuberculosis. The causative role of these mutations in mycobacterial virulence should be validated in future study.

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“…These additional genetic descriptions revealed great similarity of the Beijing strains isolated in Colombia with "modern" Beijing strains from Asia instead of the Pacific or Asian-African Beijing sublineages [48]. Additionally, our MDR strain that was sequenced shared the eight SNPs that were proposed to be exclusively present in Beijing MDR strains from Colombia (Table 4) [35]. On the other hand, the drug-susceptible Beijing strain only shared one mutation with another "Beijing-like" strains from Colombia (Table 3) [38].…”

Section: Plos Onementioning

confidence: 69%

“…All SNPs associated with the MDR phenotype were confirmed for the strain 38765. WGS of the MDR strain also allowed the identification of eight SNPs that had been previously reported in MDR Beijing strains from Colombia by Rodriguez-Castillo et al, [35] (Table 4). Among other relevant SNPs, both Beijing strains (38088 and 38765) exhibited an insertion of a Guanine at the position 1406760^1406761 in the Rv1258c gene.…”

Section: Plos Onementioning

confidence: 83%

Genetic profiling of Mycobacterium tuberculosis revealed “modern” Beijing strains linked to MDR-TB from Southwestern Colombia

et al. 2020

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Beijing strains of Mycobacterium tuberculosis (lineage 2) have been associated with drug-resistance and transmission of tuberculosis worldwide. Most of the Beijing strains identified in the Colombian Pacific coast have exhibited a multidrug resistant (MDR) phenotype. We sought to evaluate the clonality and sublineage of Beijing strains circulating in Southwestern Colombia. Thirty-seven Beijing strains were identified through spoligotyping out of 311 clinical isolates collected in 9 years from 2002-2010. Further analysis by MIRU-VNTR 24 loci was conducted for the Beijing strains. For sublineage classification, deletions of RD105, RD207, and RD131 and point mutations at fbpB, mutT2, and acs were evaluated. Drug-resistance associated mutations to first-and second-line anti-TB drugs were also evaluated. Additionally, two Beijing strains were Illumina-whole genome sequenced (one MDR and one drug-susceptible). Among the 37 Beijing strains characterized, 36 belonged to the SIT190 type from which 28 were MDR, four pre-extensively drug resistant (XDR) TB, and four XDR-TB. The remaining strain was SIT1 and drug susceptible. MIRU-VNTR analysis allowed the identification of three Beijing clusters and two unique strains. Beijing strains were confirmed as "modern" sublineage. The mutations rpoB S531L and katG S315T were the most common among MDR strains. Moreover, the two strains evaluated by whole genome sequencing (WGS) shared most of the genetic features with the sublineage 2.2.1 "modern" Beijing previously characterized from Asian strains. WGS analysis of the MDR strain revealed the presence of eight SNPs previously reported in other MDR "Beijing-like" strains from Colombia. The presence of "modern" Beijing strains in Southwestern Colombia, most of them with MDR phenotype, suggests a different origin of this M. tuberculosis sublineage compared to other Beijing strains found in neighboring South American countries. This work may serve as a genetic baseline to

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

Cited by 24 publications

References 72 publications

Genetic profiling ofMycobacterium tuberculosis“modern” Beijing strains from Southwest Colombia

Genetic profiling ofMycobacterium tuberculosis“modern” Beijing strains from Southwest Colombia

Comparative Whole-Genomic Analysis of an Ancient L2 Lineage Mycobacterium tuberculosis Reveals a Novel Phylogenetic Clade and Common Genetic Determinants of Hypervirulent Strains

Genetic profiling of Mycobacterium tuberculosis revealed “modern” Beijing strains linked to MDR-TB from Southwestern Colombia

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