Tuberculosis (TB), caused by bacteria of the Mycobacterium tuberculosis complex (MTBC), remains a global threat to human health, which causes an estimated 2 million deaths annually (1). No horizontal gene transfer has been reported in MTBC, and the genome is more highly conserved than other pathogenic bacteria (2). Nevertheless, genotyping tools have recently identified several polymorphisms in the MTBC genome that have provided insight into its evolution. Three major groups of MTBC genome alterations have been reported: single nucleotide polymorphisms (SNPs), large sequence polymorphisms (LSPs), and polymorphisms within repetitive sequences such as variable number tandem repeats (VNTRs). The first 2 groups mark irreversible genetic events and can be used to construct phylogenies for M. tuberculosis (2-6). An association between geographic region and M. tuberculosis families, defined by specific polymorphisms, has been demonstrated. This geographic structuring producing genetically, and perhaps phenotypically, distinct MTBC populations may contribute to differences in clinical features such as severity of disease or prevalence of extrapulmonary disease (6-8) and should be considered during the development of new drugs and vaccines.
Sreevatsan et al. divided MTBC strains into 3 principal genetic groups (PGG1-PGG3) based on SNPs in codon 463 of katG and codon 95 of gyrA (2). More recently, on the basis of polymorphisms in the oxyR, katG, and rpoB genes, strains have been divided into 5 lineages (I-IV and M. bovis); lineages I, III, and IV represent subgroups within PGG1, and lineage II corresponds to PGG 2 and 3 (7). By combining these markers with LSPs RD239, RD105, RD750, RD711, and RD702, a small 7bp deletion in the pks15/1 gene and other SNPs, Gagneaux and Small were able to confirm these M. tuberculosis lineages and 2 lineages of M. africanum (6). The deletions RD9 and TbD1 are useful phylogenetic markers for other members of MTBC complex and ancestral M. tuberculosis strains (3). The loss and acquisition of repeats or spacers in the direct repeats region (9) does not appear to limit their value in biogeographic and phylogenetic studies (10,11).
Genotypic variation of MTBC strains at various geographic settings and significant associations between certain allelic variants at VNTR loci, MTBC lineages, and spoligotyping families have been reported (7,12-15). However, most studies used single genotyping methods on small populations or convenience samples. Population-based studies have focused primarily on areas of low- to middle-TB incidence, and it is unclear whether the results are universally applicable (16-18). Larger population-based studies on geographically diverse populations are needed to establish the phylogenetic, epidemiologic, and clinical relevance of such associations.
London accounts for nearly half of all TB cases in the United Kingdom ([approximately equal to] 3,300 cases in 2006; incidence rate 44.8/100,000). Because 75% of these TB patients were born abroad (19), (Health Protection Agency update; www. hpa.org.uk), and clinical signs of disease develop within 2 to 3 years of arrival, we believe that the multicultural and diverse community in London provides a unique setting for studying the global biodiversity of MTBC. We aimed to establish whether MTBC isolates circulating in the London...