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Multicenter Study
. 2010 Feb;16(2):272-80.
doi: 10.3201/eid1602.091032.

Associations between Mycobacterium tuberculosis strains and phenotypes

Timothy Brown  1 , Vladyslav Nikolayevskyy, Preya Velji, Francis Drobniewski
Affiliations
Multicenter Study

Associations between Mycobacterium tuberculosis strains and phenotypes

Timothy Brown et al. Emerg Infect Dis. 2010 Feb.

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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Figures

Figure 1
Figure 1
Mycobacterium tuberculosis complex lineages as determined by Gagneux et al. (6) and Baker et al. (7) defined by mycobacterial interspersed repetitive unit codes. MBOV, M. bovis; LAM, Latin American; CAS, Central Asian; EAI, East African–Indian; BCG, bacillus Calmette-Guérin; MAFR, M. africanum. The X, T, LAM, S, and Haarlem families are European American types.
Figure 2
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.
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