A newly discovered antibiotic kills bacteria by a dual attack mechanism

Work done in the lab of Dr. Markus H. Weingarth at Utrecht University, the Netherlands

About author

Rhythm Shukla earned her BS-MS degree from the Indian Institute of Science Education and Research (IISER), Mohali, India. Subsequently, she moved to the Netherlands and joined Dr. Markus Weingarth’s lab at the Utrecht University for her PhD in 2019 to study the mechanism of action of new antibiotics like Teixobactin. During her PhD, she worked on a synthetic analogue of Teixobactin which was published in Nature Communications 2020 and this work was very well received by the community. She recently published her research findings on the natural Teixobactin, done in collaboration with the Prof. Kim Lewis’s lab from the Northeastern University, USA in the journal Nature and this work is considered to be a paradigm shift in the antibiotic field. Here, Rhythm talks about her article “Shukla, R., Lavore, F., Maity, S. et al. Teixobactin kills bacteria by a two-pronged attack on the cell envelope. Nature. https://doi.org/10.1038/s41586-022-05019-y” published in (2022).

Interview

How would you explain your research outcomes to the non-scientific community?

My research findings led to the identification of the mechanism of action of Teixobactin, a novel antibiotic that kills bacteria via a dual action mechanism. It targets an important lipid in the membrane of bacterial cells which cannot be replaced once bound and subsequently results in killing the bacteria by forming deadly fibrils and breaking open the bacterial surface. We used the state-of-the-art solid-state NMR and microscopy techniques directly on the bacterial membranes to fill the major gap of knowledge in the field. Since the experiments were done in the native environment of the drug, we can present a highly accurate structure of the complex directly in the bacterial membranes which would be more useful to pursue Teixobactin for clinical trials.

How do these findings contribute to your research area?

Understanding the mechanisms of action for the new classes of antibiotics is important to study antimicrobial resistance. Teixobactin , a first of its kind drugs discovered after a gap of 30 years, not only targets a molecule in the cell membrane but also forms bigger structures which results in opening the membrane. These findings have bridged the existing gap of knowledge in antibiotic research by studying the antibiotics in their native environment.

“Our findings have bridged the existing gap of knowledge in antibiotic research by studying the antibiotics in their native environment.”

What was the exciting moment during your research?

While using advanced microscopy techniques such as high-speed AFM, when we were able to observe the formation of fibrils and massive dents in the membrane, it was probably the most exciting part of our research.

What do you hope to do next?

We plan to use this methodology to study drugs in their native environment and understand their mechanisms to develop an ideal drug template to design the antibiotics in future.

Where do you seek scientific inspiration from?

The current situation of antimicrobial resistance is a threat to global health. We need to discover new antibiotics against which bacteria cannot gain resistance. Understanding how these antibiotics work can help us design future drugs which will help us to solve this problem. We sought to achieve this through our study on a very promising antibiotic, Teixobactin.

Reference

Shukla, R., Lavore, F., Maity, S. et al. Teixobactin kills bacteria by a two-pronged attack on the cell envelope. Nature (2022). https://doi.org/10.1038/s41586-022-05019-y

Copy Editor

Neha Varshney

Postdoctoral Researcher at Ludwig Institute for Cancer Research

Neha is currently a Postdoctoral Researcher at Ludwig Institute for Cancer Research. She completed her PhD from JNCASR India.

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