Mycobacterial Diseases
Open Access

Genetic Strains of Tuberculosis and their Role in Drug Resistance

Nachega Agosto^{* *}Correspondence: Nachega Agosto, Department of Microbiology, University of Hamburg, Hamburg, Germany, Email:

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Description

Mycobacterium tuberculosis (M. tb), the bacterium responsible for Tuberculosis (TB), has demonstrated significant genetic diversity across its strains, influencing the disease's epidemiology, transmission dynamics, and treatment outcomes. One important aspect of this genetic diversity is its correlation with Multidrug Resistant Tuberculosis (MDR-TB), which is defined as resistance to at least isoniazid and rifampin, the two most potent first-line anti-TB drugs. Understanding the relationship between M. tuberculosis genotypes and drug resistance is essential for effective TB control and the development of targeted therapeutic strategies. Different M. tuberculosis lineages, such as the Beijing and East-African Indian (EAI) strains, show varying propensities for developing drug resistance. These genetic variations influence not only resistance patterns but also transmission rates and clinical outcomes. Studying these associations provides insights into MDR-TB evolution and informs the design of tailored diagnostic tools and treatment protocols.

Genotypes of Mycobacterium tuberculosis

M. tb is classified into various lineages based on genetic markers, such as Single Nucleotide Polymorphisms (SNPs) and Regions of Difference (RDs). These lineages include, lineage 1 (Indo- Oceanic), lineage 2 (East Asian, including Beijing strains), lineage 3 (East-African Indian), lineage 4 (Euro-American), lineage 5 and 6 (West African, Mycobacterium africanum), lineage 7 (Ethiopian). Each lineage exhibits unique geographic distributions and pathogenic characteristics. Among these, the Beijing genotype (lineage 2) has drawn particular attention due to its strong association with drug resistance and increased transmissibility. The Beijing genotype is prevalent in East Asia but has also spread globally, contributing significantly to MDRTB cases. Its success is attributed to its adaptability, ability to evade host immune responses, and higher mutation rates under drug pressure. Studies suggest that this lineage may be more virulent, leading to severe disease outcomes. Targeted public health interventions are essential to mitigate its impact on TB control efforts.

Beijing genotype and multidrug resistance

The Beijing genotype is one of the most studied M. tuberculosis genotypes because of its global prevalence and its alarming correlation with MDR-TB. Several studies have shown that Beijing strains are more likely to acquire and transmit drug resistance mutations compared to other genotypes. Key factors contributing to this phenomenon include:

Genetic mutability: Beijing strains exhibit higher mutation rates, increasing their likelihood of developing drug resistance.

Immune evasion: These strains can evade host immune responses more effectively, facilitating their persistence and transmission.

Adaptation to treatment pressures: Beijing strains have shown an enhanced ability to survive under antibiotic pressure, leading to the selection of resistant variants.

Other genotypes and drug resistance

While the Beijing genotype is most strongly linked to MDR-TB, other genotypes also demonstrate varying levels of association with drug resistance. For instance, strains from Lineage 4 (Euro- American) have shown moderate correlations with drug resistance in certain settings, particularly in high-burden regions. The role of Lineage 1 and Lineage 3 in MDR-TB appears less pronounced, but localized studies indicate that these genotypes can contribute to resistance in specific geographic or demographic populations. Genotypes from Lineage 5 and Lineage 6 (Mycobacterium africanum) are primarily confined to West Africa and exhibit unique resistance patterns, often influenced by regional factors such as treatment practices and healthcare access. Additionally, the recently identified Lineage 7 in Ethiopia is being studied for its potential contributions to resistance, although data remains limited. Understanding these lineage-specific variations is significant for customizing TB control measures. Geographic and population-specific studies are essential to uncover the complex interplay between genotypes and drug resistance, ultimately improving the global response to MDR-TB.

Mechanisms of multidrug resistance

The genetic mutations responsible for MDR-TB are welldocumented. Resistance to rifampin is primarily caused by mutations in the rpoB gene, while resistance to isoniazid often involves mutations in the katG gene or the inhA promoter region. Specific genotypes, such as the Beijing strain, are more likely to harbor these mutations, underscoring their link to MDR-TB. Additionally, mutations in the embB gene contribute to ethambutol resistance, while mutations in the pncA gene are associated with pyrazinamide resistance. These genetic alterations often arise under selective pressure from inadequate or incomplete treatment regimens. The prevalence of specific mutations varies geographically, reflecting local epidemiological and treatment practices. Molecular diagnostics, such as GeneXpert and line-probe assays, have been instrumental in rapidly identifying these mutations, enabling timely management of MDR-TB cases. Early detection and tailored treatment strategies are essential to curb the spread of resistant strains.

Conclusion

The genetic diversity of M. tuberculosis plays an important role in the emergence and spread of MDR-TB. Genotypes such as the Beijing strain have proven to be particularly problematic, exhibiting strong correlations with drug resistance and increased transmission. By integrating genotypic data into TB control strategies, healthcare systems can enhance the detection, treatment, and prevention of MDR-TB, ultimately improving patient outcomes and reducing the global TB burden.