Tuberculosis Research Team

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Tuberculosis Research Team

Overview : Industrial Tuberculosis Research team, Industrial Medical Molecular Biotechnology Research Group conducts researches involved in Mycobacterium tuberculosis (MTB), an etiology of tuberculosis (TB), using the microbiological and molecular biological tools to solve TB problems in Thailand. Three main aspects of researches are as follows: (1) Development of TB diagnosis, (2) Epidemiological study of M. tuberculosis in Thailand, and (3) Development of new TB vaccine

Current status

1) Development of TB diagnosis

Research activities are focusing on identifying biomarkers related to active TB and latent TB infection presence in both human and animals (Thai elephants and cynomolgus monkeys), defining and discovering mechanisms of anti-TB drug resistance, and studying distributions of drug-resistant genes among the M. tuberculosis isolates identified in Thailand. Interesting TB drugs are the first-line (isoniazid, rifampicin, pyrazinamide, ethambutol and streptomycin) and the second-line groups (fluoroquinolones, amikacin, kanamycin, capreomycin, ethionamide, para-aminosalicylic acid and clarithromycin). These research studies would be applicable for further TB diagnosis development.

1.1) Drug-resistant TB and molecular mechanisms of drug resistance

Current researches mainly focus on the distribution of drug-resistant genes and new mechanisms among Thai MTB strains which are resistant to either fluoroquinolones, or streptomycin, or para-aminosalicylic acid (PAS), or new anti-TB drugs (bedaquiline and delamanid) by using the next-generation sequencing (NGS). In addition, biomarker-based assays for TB prognosis in human and animals are also under development.

1.2) Immunodiagnosis of tuberculosis

The research aim is identification of specific MTB biomarkers for screening of TB infection stages (Active-TB or Latent-TB) found in both human and animals. Here, two immunoassay methods, Multi-antigen print immunoassay (MAPIA) and Enzyme-linked immunosorbent assay (ELISA), are being applied and developed.

2) Epidemiological study of M. tuberculosis isolates in Thailand

Research activities are focusing on epidemiological study of MTB isolates in Thailand. Their genetic diversity, TB outbreak, drug resistance pattern and clinical factors related to TB transmission and virulence will be investigated and studied by using the next-generation whole genome sequencing technology along with clinical and epidemiological information from patients. In addition, the pipeline for whole genome sequence analysis has been developed and used for MTB genotyping and

prediction of drug resistance. Databases of single nucleotide polymorphisms (SNPs) specific for MTB genotypes and drug resistance have also been constructed. Finally, these studies will provide basic information for epidemiological study, which would be useful for studying transmission dynamics of MTB in community and prediction of treatment outcome.

3) Development of new TB vaccine

Research activities aim to develop a new TB vaccine. Recombinant Mycobacterium bovis BCG Tokyo 172-1 vaccine strains highly expressed of active- and latent-specific MTB antigens are under construction and evaluation.

- TB diagnostic methods in animals (Thai elephants and cynomolgus monkeys)
- Molecular methods for detection of drug-resistant TB
- Basic knowledge involving drug-resistant TB and its associated genes
- Pipeline for TB whole genome sequence analysis and its applications