UK researchers are developing simplified synthetic versions of teixobactin, which are capable of killing drug-resistant bacteria

Destruction of a bacterium visualisation_104491749_Kateryna_Kon

UK researchers have made significant progress towards developing a new class of synthetic antibiotics capable of killing drug-resistant bacteria, including methicillin-resistant Staphylococcus aureus (MRSA).

The antibiotics being developed are simplified synthetic versions of teixobactin, a molecule utilised by producer bacteria to eliminate other bacteria in soil. The cell wall synthesis inhibitor, teixobactin, was first identified in 2015 from a screen of uncultured bacteria as a potential antibiotic without detectable resistance. 

Several cases of sepsis and pneumonia are a direct consequence of untreatable antibiotic resistant infections. An estimated 12,000 individuals in the UK die each year from antibiotic resistance, a number comparable to breast cancer deaths. According to the Review on antimicrobial resistance (AMR), this figure is likely to rise to 10 million deaths annually by 2050 if the problem is not addressed.

Former UK Prime Minister David Cameron said in 2014, when the Review on AMR was commissioned: ‘If we fail to act, we are looking at an almost unthinkable scenario where antibiotics no longer work and we are cast back into the dark ages of medicine.’

Synthetic teixobactin: last line of defence against superbugs

The ground-breaking research was led by Dr Ishwar Singh, an expert in antimicrobial drug discovery and development and medicinal chemistry at Liverpool’s Centre of Excellence in Infectious Diseases Research. The University of Lincoln also contributed to the project. The team found that synthetic teixobactin derivatives were capable of killing a wide range of antibiotic-resistant pathogenic bacteria, including MRSA, in mouse models.

Furthermore, an accumulation of the antibiotic was observed at infection sites for up to 24 hours in amounts much higher than that required to kill the resistant organisms. This highlights the possibility of a single daily dose of synthetic teixobactin to manage serious systemic bacterial infections.

The researchers found that synthetic teixobactins could remain stable at room temperature for years, thereby eliminating the need for cold-chain distribution and storage.

Dr Singh and colleagues have also found a way to boost the production the synthetic antibiotics at an economic cost by replacing certain amino acids on the molecule with low-cost, commercially available alternatives.

Dr Singh said: ‘Our ultimate goal is to have a number of viable drugs from our modular synthetic teixobactin platform which can be used as a ‘last line of defence’ against superbugs to save lives currently lost due to AMR.’

Next steps: safety testing

Health and Social Care Secretary, Sajid Javid said: ‘It is fantastic to see such innovative work like this happening in the UK—another clear example of this country being at the forefront of scientific advancements which can benefit people across the world.’

Innovation Lead for AMR and Vaccines at Innovate UK, Dr Phil Packer said: ‘This has been an excellent project and we sincerely hope this work will continue and go much further.’ Dr Packer emphasised that, although there is a lot of ongoing research in the AMR space, much of it revolves around modifying existing classes of molecules. ‘The modified molecules could eventually succumb to AMR since the scaffold molecules are familiar to the pathogens.’

Dr Singh said the project’s next steps will be to focus upon the central benefit of synthetic teixobactin to overcome multi-drug resistant bacteria in different disease models, scale up process, and conduct safety testing, which—if successful—could potentially be used in hospitals as an investigational new medicine and be turned into a drug fit for treating resistant bacterial infections globally.

This article originally appeared on Medscape, part of the Medscape Professional Network.

Credit:

Lead image: Kateryna_Kon/stock.adobe.com
Image 1: Kateryna_Kon/stock.adobe.com