We summarise a recent review, published in Frontiers in Microbiology, that explored how modern -omics technologies can facilitate the drug discovery process for tuberculosis treatment.
Tuberculosis
Tuberculosis (TB) is an infectious disease caused by the bacterium Mycobacterium tuberculosis. According to the WHO, TB is one of the top 10 causes of death worldwide, killing 1.5 million every year. The pathogens’ thick cell wall, complex life cycle and prolonged periods of latency, make it very difficult to eradicate.
The standard treatment of tuberculosis requires 6–20 months, depending on the drug susceptibility of the infecting strain. A cocktail of antibiotics must be taken to avoid rapid pathogen drug resistance. However, the emergence of drug-resistant strains is a major problem for current therapies, prompting the need to search for new antitubercular compounds.
Drug development
The drug discovery process is long and costly. The main cause of failures in the clinical development of drugs is its insufficient effectiveness. Although funding for the prevention, diagnosis and treatment of TB has doubled since 2006, it is still insufficient. Pharmaceutical companies mainly research new antibiotics – most of which is carried out by small and medium-sized institutions. Large pharma companies account for 3% of research. The costs of developing a new drug are high, with little prospect of reimbursement from developing countries where tuberculosis is most prevalent. This has led experts to incorporate new technological solutions, such as -omics technologies, to facilitate the introduction of new, effective and safe drugs into the market.
Harnessing -omics technologies
Below are some of the ways -omics technologies and genetic manipulation of organisms can increase our understanding of the mechanisms of action of antibiotics and allow the evaluation of drugs.
- Genomics: One way to identify drug targets is to look for drug resistance mutations, which can be done by whole-genome sequencing of the resistant strain. Information regarding the genomic DNA sequence can provide the basis for genetic manipulation. This allows researchers to assess the impact of the mutations and evaluate chemical compounds against specific targets.
- Transcriptomics: To identify an antibiotic’s mode of action, researchers can look at changes in the metabolism, growth and morphology of bacteria. Researchers can obtain transcriptomic data through microarrays or RNA-seq. It can enable predictions of antibiotic classes based on transcriptomic responses.
- Metabolomics: This approach is useful to find new targets and understand compounds’ mode of action. Analysing the network of metabolites and the interactions between them can provide insight into cellular processes. Lipidomics is a separate part of metabolomics. Analysis of cell lipid content changes can lead to the identification of key pathways in lipid biosynthesis.
Summary
There is a growing demand for new antibiotics, particularly as multi-drug resistant strains continue to emerge. This demand has stimulated the development of research methods that broaden the knowledge about biological processes occurring in bacterial cells. Understanding these processes enables more effective identification of antitubercular compounds. Emerging -omics technologies have opened opportunities to identify safer drugs that are less prone to generation of drug resistance. When combined, these technologies provide a more holistic view of drug utility.
Image credit: By Image Team – canva.com
