Compounds show promise in search for tuberculosis antibiotics

Compounds tested for their potential as antibiotics have demonstrated promising activity against one of the deadliest infectious diseases – tuberculosis (TB).

Researchers from the John Innes Centre evaluated two compounds with antibacterial properties, which had been produced by the company Redx Pharma as antibiotic candidates, particularly against TB.

TB, which is caused by the bacterium Mycobacterium tuberculosis, is often thought of as a disease of the past. But in recent years it has been increasing due, in part, to rising resistance to treatments and decreasing efficacy of vaccines.

One strategy in the search for new treatments is to find compounds that exploit well-known existing targets for drugs such as the bacterial enzyme DNA gyrase. This member of the DNA topoisomerase family of enzymes is required for bacterial DNA functionality, so compounds that inhibit its activity are much sought after as antibiotic candidates.

Using X-ray crystallography, the team elucidated the molecular details of the action of the compounds against their target.

Surprisingly, a very common mutation in DNA gyrase that causes bacteria to be resistant to a related group of antibiotics, the aminocoumarins, did not lead to resistance to the compounds under scrutiny here.

“We hope that companies and academic groups working to develop new antibiotics will find this study useful. It opens the way for further synthesis and investigation of compounds that interact with this target,” says Professor Tony Maxwell one of the authors of the study which appears in the Journal of Antimicrobial Chemotherapy.

To date, efforts to develop new treatments for TB have been unsuccessful, with current treatments having been used for over 50 years.

World Health Organisation (WHO) figures reveal that each day over 4000 people die from TB and 300,000 people fall ill from the disease. Nearly 500,000 people fell ill with drug-resistant TB in 2018.

Professor Maxwell says: “Antimicrobial resistance (AMR) is now well-recognised as one of the biggest problems facing us in the in the 21st Century. If we don’t find solutions to it soon, we could be looking at epidemics of bacterial disease going forward. People know about the bubonic plague and other such terrible pestilence through studying history but it’s not overstating the case that bacterial diseases of this sort could reemerge if we do not have effective antibiotics. We must find a way of bringing together expertise from the academic and business sector towards decisive action.”

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The study appears in the Journal of Antimicrobial Chemotherapy.

Funding for the study came from BBSRC, Wellcome Trust, Redx Pharma.

About the John Innes Centre

The John Innes Centre is an independent, international centre of excellence in plant science and microbiology.

Our mission is to generate knowledge of plants and microbes through innovative research, to train scientists for the future, to apply our knowledge of nature’s diversity to benefit agriculture, the environment, human health, and wellbeing, and engage with policy makers and the public.

To achieve these goals we establish pioneering long-term research objectives in plant and microbial science, with a focus on genetics. These objectives include promoting the translation of research through partnerships to develop improved crops and to make new products from microbes and plants for human health and other applications. We also create new approaches, technologies and resources that enable research advances and help industry to make new products. The knowledge, resources and trained researchers we generate help global societies address important challenges including providing sufficient and affordable food, making new products for human health and industrial applications, and developing sustainable bio-based manufacturing.

This provides a fertile environment for training the next generation of plant and microbial scientists, many of whom go on to careers in industry and academia, around the world.

The John Innes Centre is strategically funded by the Biotechnology and Biological Sciences Research Council (BBSRC), and is supported by the John Innes Foundation through provision of research accommodation, capital funding and long-term support of the Rotation PhD programme.

For more information about the John Innes Centre visit our website http://www.jic.ac.uk

About BBSRC

The Biotechnology and Biological Sciences Research Council (BBSRC) is part of UK Research and Innovation, a non-departmental public body funded by a grant-in-aid from the UK government.

BBSRC invests in world-class bioscience research and training on behalf of the UK public. Our aim is to further scientific knowledge, to promote economic growth, wealth and job creation and to improve quality of life in the UK and beyond.

Funded by government, BBSRC invested £498 million in world-class bioscience in 2017-18. We support research and training in universities and strategically funded institutes. BBSRC research and the people we fund are helping society to meet major challenges, including food security, green energy and healthier, longer lives. Our investments underpin important UK economic sectors, such as farming, food, industrial biotechnology and pharmaceuticals.

More information about UK Research and Innovation.

More information about BBSRC, our science and our impact.

More information abou ?BBSRC strategically funded institutes.

Media Contact
Adrian Galvin
[email protected]
http://dx.doi.org/10.1093/jac/dkaa286

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