ReviewMycobacterium tuberculosis Beijing genotype: A template for success
Introduction
A third of the world’s population is estimated to be infected with Mycobacterium tuberculosis and over 9 million tuberculosis (TB) cases are diagnosed annually, resulting in almost 2 million deaths every year.170 This makes TB the infectious disease with the highest adult mortality rate. TB accounts for more than a quarter of all preventable adult deaths in developing countries and for a third of HIV/AIDS related deaths. Factors that probably influence the worldwide prevalence are the escalating numbers of HIV/AIDS cases, emergence of drug-resistant TB (especially multidrug-resistant (MDR) and extensively drug-resistant (XDR)), the increase in population mobility and failure to implement effective TB control.
M. tuberculosis presents with a variety of clinico- and histopathological features (duration of disease, severity, extension and anatomic distribution of lesions (localised or generalised)) and manifestion of disease in different human host populations (some geographical areas are more affected than others).25, 68 However, despite ongoing research, the mechanisms governing pathogenicity and the factors influencing the degree of disease variability remain largely unknown; several host factors (i.e. malnutrition, homelessness, and genetic predisposition) and environmental factors (i.e. exposure to environmental mycobacteria, overcrowding) have been suggested. However, there is substantial evidence to suggest that bacterial factors (i.e. genetic variation in the mycobacterium) also contribute to the variability of disease presentation, frequency of transmission and treatment outcome.22, 25, 157, 158
To date, several M. tuberculosis genotypes have been described. The Haarlem genotype, which has been responsible for a prolonged outbreak of MDR-TB in Argentina, represents about 25% of isolates in Europe, Central America and the Caribbean.18 The recently discovered RDRio (a Latin American–Mediterranean sublineage) accounts for 37% of the total TB burden in Brazil and central Southern Africa.29, 87 On the other hand, the Beijing genotype has been found to be the most frequently observed strain genotype of M. tuberculosis to cause disease globally.61 Thus, understanding the genetic variations among the different genotypes could help clarify their contribution to phenotypic differences.
Section snippets
Introduction to the Beijing genotype strains
Strains of the M. tuberculosis Beijing genotype was first identified by van Soolingen et al. (1995) after analysing M. tuberculosis isolates collected from 1992–1994 from TB patients resident in the People’s Republic of China and Mongolia.165 A comparison between IS6110 RFLP fingerprints from the East Asian region showed that strains with this genotype were more frequently observed in East Asia compared to more distant regions, suggesting that these strains may have originated and spread from
Genotypic features of the Beijing genotype strains
Strains of the Beijing genotype have definitive genotypic characteristics (Table 2) which differentiate them from all other M. tuberculosis genotypes. Beijing genotype strains are members of principal genetic group (PGG) 1,140 Spoligotype S00034 or ST1,75 Lineage 110 and Cluster II63 while according to large sequence polymorphism (LSP)-based analysis they form part of the East Asian lineage57 and can be differentiated from other genotypes according to a set of unique non-synonymous single
Phenotype of the Beijing genotype strains
Numerous lines of evidence suggest that members of the Beijing genotype possess unique phenotypic characteristics. Importantly, many studies have shown that they may be hypervirulent compared to most other strain genotypes.1, 12, 61, 97, 119 This hypervirulence may be explained by differences in their interaction with the host immune system.97, 121, 130 Below we review the evidence for hypervirulence of the Beijing genotype as well as other Beijing-associated phenotypic characteristics such as
Conclusion
A prominent theme emerging from the results of the studies in the present review is that the genetic background of M. tuberculosis strains does influence the risk of disease pathology and progression. Based on the data accumulated it is clear that virulence of the Beijing genotype strain is not determined by a single characteristic but is the result of many unique, intricate and dynamic interactions between host and the pathogen that ultimately arise from alterations in the pathogen’s genome.
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Competing interests
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Present address: Department of Microbiology and Immunology, University of Melbourne, Victoria 3010, Australia.