Natural Antibiotic Shows Promise as New Class of Drug

Scientists from the University of Liverpool and the University of Utrecht are working together to develop a viable drug based on a new class of potent natural antibiotic capable of killing superdrugs.

Teixobactin was hailed as a “game changer” when it was discovered in 2015 due to its ability kill multi-drug resistant bacterial pathogens such as MRSA without developing resistance. If made suitable for humans, it would mark the first new class of antibiotic drug for 30 years.

Dr Ishwar Singh, an expert in Antimicrobial Drug Discovery and Development and Medicinal Chemistry at Liverpool’s Centre of Excellence in Infectious Diseases Research, has led pioneering research over the past six years to develop teixobactin-based viable drugs. His research team was the first in the world to successfully create simplified synthetic forms of teixobactins which are effective in treating bacterial infections in mice.

Dr Singh explained: “We know that the therapeutic potential of simplified synthetic teixobactins is immense and our ultimate goal is to have a number of viable drugs from our synthetic teixobactin platform which can be used as a last line of defence against superbugs to save lives.”

In collaboration with NMR expert Professor Markus Weingarth at the University of Utrecht, the team used high resolution solid state NMR and microscopy to show, for the first time, how synthetic teixobactins bind to lipid II (an essential component of the bacterial membrane) and kill the bacteria.

Dr Singh said: “It had been assumed that teixobactins kill the bacteria by binding to bacterial cell wall bricks such as lipid II, but never shown until now. Our work also suggests that teixobactins kill the bacteria by capturing lipid II in massive clusters, a new killing mechanism, which we were excited to discover.”

Dr Singh added: “A significant amount of work remains in the development of teixobactins as a therapeutic antibiotic for human use. Our study is a real step in right direction and opens the door for improving teixobactins and moving these toward clinic.

Dr Singh’s work received funding support from the Department of Health and Social Care, UK and Rosetrees Trust.