Resistance is…years away: New compound could delay post antibiotic era

By Gareth Macdonald contact

- Last updated on GMT

Tteixobactin could delay dawn of post-antibiotic era
Tteixobactin could delay dawn of post-antibiotic era

Related tags: Bacteria

Discovering a new antibiotic candidate and finding out how it kills superbugs without letting resistant mutants escape involved advanced chemistry according to the scientists who determined its structure.

Novobiotic Pharmaceuticals and academics from the US and Germany unveiled Teixobactin in a paper in Nature​ today, suggesting that the techniques used to find the compound are “a path towards developing antibiotics that are likely to avoid development of resistance​.”

The team – from Northeastern University and the Uni­ver­sity of Bonn used a novel technology​ – iChip –to culture the bug that makes Teixobactin, which is significant because the unnamed soil-dwelling organism had been impossible to grow in the lab before.

At present, 80% of commercially available antibiotics are derived from bacteria. However, according to lead research Kim Lewis, microbiologists have only been able to grow 1% of the world’s bugs in the lab.

In the long term, therefore, using iChip to culture the 99% of bacteria that cannot be grown in the lab may yield many potentially antibiotic compounds and eventually new drug candidates.

Structure and function

In the more immediate term, if teixobactin can be turned into a drug it may delay what the WHO calls the “post antibiotic era​,” particularly as it kills bacteria in a similar way to Vancomycin which was on the market for 30 years​ before bugs became resistant. 

Instead of killing bacterial cells by binding proteins like other antibiotics, the new compound targets highly conserved motifs of fatty acid components of the bacterial cell wall, which stops the cells multiplying.

These target lipid motifs are less prone to structural changes than proteins, meaning that it is likely to take a lot longer for bacteria like staphy­lo­coccus aureus​ and MSRA to develop resistance to teixobactin.

UK-based firm Selcia, which helped Novobiotic and the academic team elucidate teixobactin’s stereochemistry, told in-Pharmatechnologist.com that the project required high tech analysis.

Novobiotic Pharmaceuticals had determined the gross structure of teixobactin using NMR techniques, but came to Selcia to determine the stereochemistry of the 11 amino acids. In layman’s terms, that involved breaking down the natural product into the constituent amino acids and comparing with standards using a technique called Advanced Marfeys Analysis​.”

The Selcia spokesperson explained that: “As one of the amino acids was an unnatural amino acid, we had to synthesise all four diastereomers to make standards for comparison with the degradant.

Additionally, as teixobactin was found to have a 3:1 mixture of L and D isoleucines, we had to carry out partial degradation to determine the positioning of the D-amino acid.”

Antibiotic pipeline

Antibiotics have been a subject of academicresearch​. However, they have not been a focus​ for the drug industry over the past 30 years, as evidenced by the decline in the number of new drugs to be approved​ and research by organisations like the WHO​ and US CDC​.   

More recently this has changed with Big Pharma companies like Sanofi​, Roche​ and Merck & Co​ all investing in antibiotics research but, as yet, no new drugs have been developed.

This need could be a significant opportunity for Novobiotic and teixobactin particularly if Lewis’ claim the drug will be in clinical trials

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