Synthetic Antibiotic Teixobactin Shown to Be More Effective Than Established Drugs in Fighting Against Superbugs

Almost five million people lose their lives due to infections associated with antimicrobial resistance (AMR), which the World Health Organization considers as one of the top global public health and development threats. In 2019 alone, AMR is attributed to the deaths of 1.27 million global deaths, and it is expected that by 2050, 10 million more will succumb to drug-resistant infections each year. Because of this, developing new antibiotics has been a crucial area of study for healthcare researchers worldwide.

Teixobactin: A New Class of Antibiotic

At the University of Liverpool, a team of researchers has developed a new synthetic antibiotic that is more effective than established drugs against antibiotic-resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA). Their study is discussed in the paper "Development of teixobactin analogs containing hydrophobic, non-proteogenic amino acids that are highly potent against multidrug-resistant bacteria and biofilms."

In this study, the scientists investigated the potent activity of teixobactin against bacterial biofilms. It is built on pioneering research by Dr. Ishwar Singh, an expert in development, medicinal chemistry, and antimicrobial drug discovery.

Dr. Singh and his colleagues developed simplified synthetic versions of the natural molecule teixobactin. The team tested a unique library of synthetic versions of teixobactin, optimizing major features of this antibiotic to enhance its safety and efficacy, plus enabling it to be produced inexpensively at a large scale.

To do so, the researchers designed and synthesized highly potent teixobactin analogs, but they swapped out the major bottleneck building block L-allo-enduracididine with the commercially available simplified building blocks like non-proteogenic amino acids. The findings reveal that the analogs are effective against a broad range of antibiotic-resistant bacterial pathogens, including those isolated from patients and bacterial biofilms.

This study is another crucial step in adapting the natural teixobactin molecule to make it suitable for human use. According to Dr. Singh, teixobactin molecules have the potential to offer new treatment options against infections related to multi-drug resistant bacteria and biofilm. Their research provides a promising foundation for further study and opens opportunities for exploring the application of teixobactin in different health-related biofilm contexts.

Biofilms refer to the slimy layers of microorganisms that stick to wet surfaces. This aggregate of bacteria is held together by a mucus-like matrix of carbohydrates that adheres to the surface. The formation of biofilm increases the resistance of bacteria against the defense mechanisms of the body, causing up to 80 percent of infections.

How Does Teixobactin Work?

Teixobactin is a peptide-like secondary metabolite of some species of bacteria that can potentially kill some gram-positive pathogenic bacteria. It comprises several uncommon residues and a natural undecapeptide from Eleftheria terrae. It was discovered in 2015 using a new method of culturing soil bacteria through iChip technology.

As a new class of antibiotic, teixobactin works by binding to lipids II and III, which serve as important precursor molecules for forming bacterial cell walls. Since it induces the simultaneous inhibition of both peptidoglycan and teichoic acid synthesis, teixobactin makes it difficult to show antibiotic resistance.