FEB 07, 2017 6:05 PM PST

Structure of new Antibiotic Shown to be Relevant to Mode of Action

WRITTEN BY: Carmen Leitch

A new antibiotic, teixobactin, was identified a few years ago. It can kill bacteria and has not been shown resistance by pathogens. It's the first new drug taken from bacteria in many years, and seems to represent a new class of drugs. Revealing more about how it works could aid researcher striving to develop more drugs that can tackle antibiotic resistant superbugs, an emerging public health threat. A team working at the University of Lincoln, UK, has had past success creating two synthetic derivatives of teixobactin. That research group has now reported the molecular architecture of the teixobactin molecule in the the Royal Society of Chemistry journal, Chemical Communications.

Certain residues maintain a reasonably unstructured teixobactin which is imperative for biological activity / Credit: Chemical Communications

"The increasing level of antimicrobial resistance represents a major global health challenge. The discovery of the highly potent antibiotic teixobactin to cope with this growing problem has provided a much-needed impetus to antibiotic research around the world. Although teixobactin does not mitigate all problems related to antimicrobial resistance, it is a definite step in the right direction, and our research continues to work towards this vital end goal," explained team leader Dr. Ishwar Singh, of he School of Pharmacy at University of Lincoln, UK.

U.S. investigators found teixobactin in microbes that live in soil in 2015. Soil has been a rich resource for antibiotics since the 1940s. However, it's not practical to use soil to make antibiotics on a large scale; scientists have to develop methods for manufacturing these molecules so they will be useful on a large scale. This new work characterizing the structure of the molecule also provides some insight into its mode of action, and it has demonstrated powerful efficacy in mice. Researchers are working on getting it to use in humans, and this work helps pave the way.

The research team found that the antimicrobial efficacy of teixobactin is directly connected to its lack of a rigid structure. The relatively unstructured nature of the molecule is critical to how it works on the biological level. This has been confirmed by the lack of effectiveness seen in more structured types of the teixobactin antibiotic. The scientists also figured out a way to retain flexibility in the molecule through the creation of chemical derivatives. "We successfully defined the molecular structure of seven teixobactin analogues," said Singh. "This enabled us to understand the importance of the individual amino acids within the antibiotic, and to understand the contribution they each make to the molecular structures of teixobactin. We found that one particular amino acid (D-Gln) is essential and another (D-Ile) is important for maintaining the disordered structure of teixobactin, which is imperative for its biological activity."

 "By exploring the structures of different versions of teixobactin we are, for the first time, able to begin to understand how this molecule works. This knowledge will enable us to produce different forms of teixobactin more easily and on a larger scale with potentially better pharmaceutical properties," commented Taylor.

Hear more about the teixobactin antibiotic in the following video.

 

Sources: AAAS/Eurekalert via University of Lincoln, Chemical Communications

About the Author
  • Experienced research scientist and technical expert with authorships on over 30 peer-reviewed publications, traveler to over 70 countries, published photographer and internationally-exhibited painter, volunteer trained in disaster-response, CPR and DV counseling.
You May Also Like
MAY 03, 2021
Cell & Molecular Biology
Are Retrons the Next CRISPR?
MAY 03, 2021
Are Retrons the Next CRISPR?
After being identified in the 1980s, it was thought that retrons were just an odd feature of some bacterial cells. But e ...
MAY 04, 2021
Cell & Molecular Biology
A Potential Weakness in SARS-CoV-2 is Caught on Video
MAY 04, 2021
A Potential Weakness in SARS-CoV-2 is Caught on Video
You can see the spike protein of the virus in action in this video.
MAY 16, 2021
Cell & Molecular Biology
Another Piece of the Lyme Puzzle is Solved
MAY 16, 2021
Another Piece of the Lyme Puzzle is Solved
Over the past 20 years, Lyme has gone from a virtually unknown disease to the most reported vector-borne illness in the ...
MAY 18, 2021
Cell & Molecular Biology
Cilia are Discovered to be Crucial to the Lymphatic System
MAY 18, 2021
Cilia are Discovered to be Crucial to the Lymphatic System
In recent years, researchers have been learning more about why cellular antennas called cilia are so important. Cilia ca ...
MAY 25, 2021
Cell & Molecular Biology
A simplified high-throughput protein expression system
MAY 25, 2021
A simplified high-throughput protein expression system
Protein synthesis, protein engineering, and synthetic biology researchers can research their protein of interest using e ...
JUN 15, 2021
Immunology
Secrets of Immune Cell Movement Revealed
JUN 15, 2021
Secrets of Immune Cell Movement Revealed
Circulating immune cells are constantly on the lookout for the presence of any pathogenic intruders in the body. Once a ...
Loading Comments...