Chapter 21 : Impact of Genetic Diversity on the Biology of Complex Strains

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The causative agents of human and animal tuberculosis (TB), and the other members of the complex, remain a major cause of human mortality and morbidity and have a massive socioeconomic impact ( ) (http://www.stoptb.org/assets/documents/events/meetings/amsterdam_conference/ahlburg.pdf). According to the latest estimates, around 100 million new tuberculosis (TB) infections, 8.5 million new notified TB cases, and 1.5 million deaths due to TB occur annually ( ).

Citation: Niemann S, Merker M, Kohl T, Supply P. 2017. Impact of Genetic Diversity on the Biology of Complex Strains, p 475-493. In Jacobs, Jr. W, McShane H, Mizrahi V, Orme I (ed), Tuberculosis and the Tubercle Bacillus, Second Edition. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.TBTB2-0022-2016
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Figure 1

Global phylogenetic structure of complex (MTBC) strains presented in a neighbor joining tree with 1,000 bootstrap replicates based on 35,577 variable sites. MTBC isolates can be classified into seven major lineages that are often composed of further geographically confined subgroups. So-called “modern” MTBC lineages (lineages 2, 3, 4) are distributed worldwide, whereas infections with “ancestral” MTBC strains are mainly restricted to western and eastern Africa. (Sequence data compiled from Comas et al. [ ] and Merker et al. [ ]).

Citation: Niemann S, Merker M, Kohl T, Supply P. 2017. Impact of Genetic Diversity on the Biology of Complex Strains, p 475-493. In Jacobs, Jr. W, McShane H, Mizrahi V, Orme I (ed), Tuberculosis and the Tubercle Bacillus, Second Edition. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.TBTB2-0022-2016
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Figure 2

Phylogenetic reconstruction of the MTBC Beijing lineage population. Midpoint-rooted maximum-likelihood tree based on 110 genomes and a total of 6,001 concatenated SNPs. Characteristic mutations differentiating modern and ancestral Beijing strain types are mapped on the tree— encoding p.Arg48Gly (branch a), encoding p.Arg37Leu (branch b), and encoding p.Gly58Arg (branch c)—as is the absence of the RD181 and RD150 regions of difference. Black squares correspond to strains with an MDR or XDR phenotype, and a number sign indicates strains lacking drug susceptibility test information. Numbers on branches correspond to bootstrap values. The tree topology remains the same when H37Rv is used as an outgroup (Merker et al. [ ]).

Citation: Niemann S, Merker M, Kohl T, Supply P. 2017. Impact of Genetic Diversity on the Biology of Complex Strains, p 475-493. In Jacobs, Jr. W, McShane H, Mizrahi V, Orme I (ed), Tuberculosis and the Tubercle Bacillus, Second Edition. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.TBTB2-0022-2016
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Figure 3

Geographical distribution of nearly 5,000 clinical Beijing (i.e., lineage 2) isolates (data from Merker et al. [ ]). Evolutionary ancestral Beijing strains are mainly dominating in East Asia, the likely origin of this MTBC lineage, whereas modern Beijing strains are globally distributed, suggesting a more virulent phenotype. In addition, the effects of globalization also shape the diversity of MTBC strains in different settings, yet with unknown consequences on host-pathogen interactions and tuberculosis progression (world map from flickr.com).

Citation: Niemann S, Merker M, Kohl T, Supply P. 2017. Impact of Genetic Diversity on the Biology of Complex Strains, p 475-493. In Jacobs, Jr. W, McShane H, Mizrahi V, Orme I (ed), Tuberculosis and the Tubercle Bacillus, Second Edition. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.TBTB2-0022-2016
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