Synthetic antibiotics could unleash the ability to kill drug-resistant superbugs and tackle the antimicrobial resistance (AMR) crisis.
A revolutionary discovery by a team of scientists from University of Liverpool could revolutionize the future of treating bacterial infections with a new class of synthetic antibiotics that have been shown to kill superbugs, including MRSA, without detectable resistance.
The team developed a simplified synthetic antibiotic based on the teixobactin molecule, which is used by producer bacteria to kill other bacteria in the soil. They developed and tested a unique selection of synthetic antibiotic varieties, optimizing key features of the drug to improve its efficacy and safety, while developing it at low cost on a large scale.
Health and Social Care Secretary Sajid Javid said: “It’s fantastic to see such innovative work like this happening in the UK – another clear example of this country being at the cutting edge of scientific advances that can benefit people around the world.”
Pioneering research on synthetic antibiotics
Principal Investigator Dr. Ishwar Singh said, “The introduction of synthetic diversity to generate the synthetic teixobactin library is important to overcome the high failure rates associated with the next steps in drug development.”
This new investigation builds on previous research by Dr Singh, an expert in antimicrobial drug discovery and development and medicinal chemistry at the Center of Excellence in Infectious Disease Research (CEIDR) in Liverpool. This program was implemented by Innovate UK on behalf of DHSC to create five lead compounds for future use in the fight against antimicrobial resistance.
Research has demonstrated that a simplified version of the teixobactin molecule in the new synthetic antibiotic can kill a range of bacteria present in human patients, where current antibiotics fail. In the future, patients could be treated with one dose of teixobactin daily for life-threatening resistant systemic bacterial infections. The new synthetic antibiotic is robust and stable at room temperature for years, therefore does not require a cold chain for distribution and storage.
Scaling production at lower cost
The synthetic antibiotic is designed to be affordable to produce. Researchers replaced certain amino acids in teixobactin with low-cost, commercially available alternatives, resulting in a 2,000-fold reduction in material cost, while improving efficacy and safety. Researchers have developed highly efficient solid-phase synthesis using automation, accelerating a single coupling step from 30 hours to just 10 minutes with high yields.
Additionally, the team optimized the preparation to increase the yield from 30mg to 1g and beyond. The process can now be scaled for application up to a scale of 1 kg or more, simply by increasing the scale and size of the reactor. Scalability is an important key element for commercial production to realize the therapeutic potential of synthetic antibiotics.
Dr Singh said: “Our motivation is to adapt the natural teixobactin molecule and make it suitable for human use. It’s a journey. Through this project, we have demonstrated that we can manufacture synthetic molecules at low cost and with high safety, which potently kill resistant bacteria in mice. The advantage of synthetic diversity is that we can select or deselect properties and modify molecules to impact potency and other desirable drug-like qualities. Our ultimate goal is to have a number of viable drugs from our modular synthetic teixobactin platform that can be used as a “last line of defense” against superbugs to save lives currently lost due to AMR.
“Our next steps will be to focus on the central benefit of synthetic teixobactin in overcoming multidrug-resistant bacteria in different disease models, a scale-up process, followed by safety testing, which, if successful, could potentially be used in hospitals as an experimental test. new drug and become a suitable drug to treat resistant bacterial infections in humans in the world. We will work with colleagues at CEIDR who have expertise in antimicrobials, from drug discovery to the clinic, to develop synthetic teixobactins into viable drugs.
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