Elsevier

Tuberculosis

Volume 91, Issue 6, November 2011, Pages 510-523
Tuberculosis

Review
Mycobacterium tuberculosis Beijing genotype: A template for success

https://doi.org/10.1016/j.tube.2011.07.005Get rights and content

Summary

The diverse clinico- and histopathological features, frequency of transmission and treatment outcome of Mycobacterium tuberculosis have been associated with several environmental, host and bacterial factors. Many Mycobacterium tuberculosis genotypes have been studied in an attempt to understand the genetic variations among the different genotypes and to clarify their contribution to phenotypic differences. Strains of the Beijing genotype have been extensively investigated due to their increased ability to spread and cause disease.

Here we review the evidence of hypervirulence of the Beijing genotype as well as other Beijing-associated phenotypic characteristics such as alternate host immune modulation, clinical and pathological features, drug resistance, resistance to BCG vaccination and other epidemiological features to enhance our understanding of the contribution of pathogenic factors.

From the data collected it is clear that the genetic background of Mycobacterium tuberculosis may influence the differential induction of the immune response, drug resistance patterns and clinical, epidemiological and pathogenic features which define disease progression following infection. This highlights the importance of ongoing research into the genetic mechanisms underlying the phenotypic and genotypic characteristics of different Mycobacterium tuberculosis genotype strains. Furthermore, these findings could help to direct future drug, vaccine and diagnostic test development towards targeting critical virulence factors and to identify persons at risk for developing active disease thereby limiting transmission and the perpetuation of the tuberculosis epidemic.

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.

Funding

None.

Competing interests

None declared.

Ethical approval

Not required.

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    c

    Present address: Department of Microbiology and Immunology, University of Melbourne, Victoria 3010, Australia.

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