Drug Discovery Platform for Tuberculosis and Shigellosis
Opportunity
Tuberculosis (TB) has taken over HIV/AIDS as the leading cause of death from a single infectious agent. Although TB is curable and preventable, World Health Organisation estimates that the disease claimed 1.5 million lives and affected 10 million people in 2018. In addition, there were over 480,000 new cases of TB that displayed resistance to rifampicin. This is worrying as rifampicin, which is an antibiotic, is currently the most effective first-line drug for TB.
The pharmaceutical industry faces challenges in discovering and developing new antibiotics. Nevertheless, the TB therapeutic market is expected to grow at a CAGR of 4.6% to exceed US$1.4 billion by 2024. If health technologies can repurpose existing drugs to address the bacterial infections and tackle resistance issues, the market projection would be even larger. This may also aid the achievement of the United Nations’ Sustainable Development Goal to eliminate TB by 2030.
Technology
Macrophages are immune cells in the body that detect, engulf and destroy disease-causing bacteria or viruses known as pathogens. However, Mycobacterium tuberculosis, which causes TB, and Shigella flexneri, which gives rise to shigellosis, can hijack macrophages for their own survival and replication. Conventional antibiotics are designed to directly kill pathogens. However, as antibiotic resistance grows, host-directed therapies are showing promise as an alternative or adjunctive treatment strategy.
This invention relates to a high throughput genome-wide drug target discovery and validation platform that is able to identify and validate host components that are essential for infection by the bacteria. Using state-of-the-art gene-editing tools, this invention features a workflow with established parameters that can interrogate host genes comprehensively and unbiasedly to reveal the key immune and metabolic pathways that support the bacterial infections. By revealing the host targets that are necessary for infection, this drug discovery and validation platform offers opportunities for development of host-directed therapies. In addition, existing drugs with known mechanisms of actions can be explored for their abilities to be anti-infectives or to serve as adjunct therapeutics to antibiotics. Overall, this invention has the potential to grow the drug repertoire for managing and overcoming antimicrobial resistance for TB and shigellosis.
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