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Associations between Mycobacterium tuberculosis strains and phenotypes.

Brown T, Nikolayevskyy V, Velji P, Drobniewski F - Emerging Infect. Dis. (2010)

Bottom Line: The Beijing family was strongly associated with multidrug resistance (p = 0.0001), and VNTR allelic variants showed strong associations with spoligotyping families: >or=5 copies at exact tandem repeat (ETR) A, >or=2 at mycobacterial interspersed repetitive unit 24, and >or=3 at ETR-B associated with the East African-Indian and M. bovis strains.All M. tuberculosis isolates were differentiated into 4 major lineages, and a maximum parsimony tree was constructed suggesting a more complex phylogeny for M. africanum.These findings can be used as a model of pathogen global diversity.

View Article: PubMed Central - PubMed

Affiliation: United Kingdom Health Protection Agency, London UK.

ABSTRACT
To inform development of tuberculosis (TB) control strategies, we characterized a total of 2,261 Mycobacterium tuberculosis complex isolates by using multiple phenotypic and molecular markers, including polymorphisms in repetitive sequences (spoligotyping and variable-number tandem repeats [VNTRs]) and large sequence and single-nucleotide polymorphisms. The Beijing family was strongly associated with multidrug resistance (p = 0.0001), and VNTR allelic variants showed strong associations with spoligotyping families: >or=5 copies at exact tandem repeat (ETR) A, >or=2 at mycobacterial interspersed repetitive unit 24, and >or=3 at ETR-B associated with the East African-Indian and M. bovis strains. All M. tuberculosis isolates were differentiated into 4 major lineages, and a maximum parsimony tree was constructed suggesting a more complex phylogeny for M. africanum. These findings can be used as a model of pathogen global diversity.

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Related in: MedlinePlus

Maximum-parsimony tree constructed based on 3 independent sets of markers: large sequence polymorphisms (LSPs), single nucleotide polymorphisms (SNPs), and number of repeats in the locus 24 using the following assumptions: 1) SNPs are irreversible unique events; 2) LSPs are irreversible rare events; 3) spoligotypes are not produced by convergent events; and 4) variable number tandem repeat (VNTR) loci can both acquire and lose repeats. EAI, East African–Indian; MIRU, mycobacterial interspersed repetitive unit code; EuroAm, European American; CAS, Central Asian; MBOV, M. bovis; MAFR, M. africanum; BCG, bacillus Calmette-Guérin. The X, T, LAM, S, and Haarlem families are European American types.
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Figure 2: Maximum-parsimony tree constructed based on 3 independent sets of markers: large sequence polymorphisms (LSPs), single nucleotide polymorphisms (SNPs), and number of repeats in the locus 24 using the following assumptions: 1) SNPs are irreversible unique events; 2) LSPs are irreversible rare events; 3) spoligotypes are not produced by convergent events; and 4) variable number tandem repeat (VNTR) loci can both acquire and lose repeats. EAI, East African–Indian; MIRU, mycobacterial interspersed repetitive unit code; EuroAm, European American; CAS, Central Asian; MBOV, M. bovis; MAFR, M. africanum; BCG, bacillus Calmette-Guérin. The X, T, LAM, S, and Haarlem families are European American types.

Mentions: The deletion TbD1 was present in all EuroAm, CAS, and Beijing strains examined as well as some other M. tuberculosis isolates and absent from all M. africanum isolates. The deletion RD9 was present in all M. bovis strains as well as some EAI and most M. africanum strains but absent from all other strains. Both deletions were absent from most EAI and some M. africanum strains (Table 3). Absence of RD9 deletion and 2 copies in MIRU24 was strongly associated with EAI spoligotype (RR 15.1, 95% CI 9.49–23.89). MTBC strains with the RD9 intact and 2 copies in MIRU24 included both M. bovis and M. africanum spoligotypes, whereas strains with the RD9 intact and 1 copy in MIRU24 formed a specific group of M. africanum originating presumably from the Indian subcontinent. Using this data, and the SNP 1-MB and the MIRU24 enumeration data, we constructed a maximum-parsimony tree as shown in Figure 2.


Associations between Mycobacterium tuberculosis strains and phenotypes.

Brown T, Nikolayevskyy V, Velji P, Drobniewski F - Emerging Infect. Dis. (2010)

Maximum-parsimony tree constructed based on 3 independent sets of markers: large sequence polymorphisms (LSPs), single nucleotide polymorphisms (SNPs), and number of repeats in the locus 24 using the following assumptions: 1) SNPs are irreversible unique events; 2) LSPs are irreversible rare events; 3) spoligotypes are not produced by convergent events; and 4) variable number tandem repeat (VNTR) loci can both acquire and lose repeats. EAI, East African–Indian; MIRU, mycobacterial interspersed repetitive unit code; EuroAm, European American; CAS, Central Asian; MBOV, M. bovis; MAFR, M. africanum; BCG, bacillus Calmette-Guérin. The X, T, LAM, S, and Haarlem families are European American types.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2958017&req=5

Figure 2: Maximum-parsimony tree constructed based on 3 independent sets of markers: large sequence polymorphisms (LSPs), single nucleotide polymorphisms (SNPs), and number of repeats in the locus 24 using the following assumptions: 1) SNPs are irreversible unique events; 2) LSPs are irreversible rare events; 3) spoligotypes are not produced by convergent events; and 4) variable number tandem repeat (VNTR) loci can both acquire and lose repeats. EAI, East African–Indian; MIRU, mycobacterial interspersed repetitive unit code; EuroAm, European American; CAS, Central Asian; MBOV, M. bovis; MAFR, M. africanum; BCG, bacillus Calmette-Guérin. The X, T, LAM, S, and Haarlem families are European American types.
Mentions: The deletion TbD1 was present in all EuroAm, CAS, and Beijing strains examined as well as some other M. tuberculosis isolates and absent from all M. africanum isolates. The deletion RD9 was present in all M. bovis strains as well as some EAI and most M. africanum strains but absent from all other strains. Both deletions were absent from most EAI and some M. africanum strains (Table 3). Absence of RD9 deletion and 2 copies in MIRU24 was strongly associated with EAI spoligotype (RR 15.1, 95% CI 9.49–23.89). MTBC strains with the RD9 intact and 2 copies in MIRU24 included both M. bovis and M. africanum spoligotypes, whereas strains with the RD9 intact and 1 copy in MIRU24 formed a specific group of M. africanum originating presumably from the Indian subcontinent. Using this data, and the SNP 1-MB and the MIRU24 enumeration data, we constructed a maximum-parsimony tree as shown in Figure 2.

Bottom Line: The Beijing family was strongly associated with multidrug resistance (p = 0.0001), and VNTR allelic variants showed strong associations with spoligotyping families: >or=5 copies at exact tandem repeat (ETR) A, >or=2 at mycobacterial interspersed repetitive unit 24, and >or=3 at ETR-B associated with the East African-Indian and M. bovis strains.All M. tuberculosis isolates were differentiated into 4 major lineages, and a maximum parsimony tree was constructed suggesting a more complex phylogeny for M. africanum.These findings can be used as a model of pathogen global diversity.

View Article: PubMed Central - PubMed

Affiliation: United Kingdom Health Protection Agency, London UK.

ABSTRACT
To inform development of tuberculosis (TB) control strategies, we characterized a total of 2,261 Mycobacterium tuberculosis complex isolates by using multiple phenotypic and molecular markers, including polymorphisms in repetitive sequences (spoligotyping and variable-number tandem repeats [VNTRs]) and large sequence and single-nucleotide polymorphisms. The Beijing family was strongly associated with multidrug resistance (p = 0.0001), and VNTR allelic variants showed strong associations with spoligotyping families: >or=5 copies at exact tandem repeat (ETR) A, >or=2 at mycobacterial interspersed repetitive unit 24, and >or=3 at ETR-B associated with the East African-Indian and M. bovis strains. All M. tuberculosis isolates were differentiated into 4 major lineages, and a maximum parsimony tree was constructed suggesting a more complex phylogeny for M. africanum. These findings can be used as a model of pathogen global diversity.

Show MeSH
Related in: MedlinePlus