Teixobactin: Introduction, Mechanism of Action, Uses

Written by Acharya Tankeshwar in Bacteriology Last Updated June 2, 2021

A group of researcher published an article in “Nature” reporting the discovery of a new cell wall inhibitor, teixobactin, from a screen of uncultured bacteria grown in diffusion chambers in situ using “ iChip” technology.

This powerful new antibiotic is reported to kill an array of drug-resistant bacteria in experimental infections in mice.It is a first new class of antibiotics  discovered in decades

Many scientists think that this is a much-needed breakthrough that could lead to a whole new class of disease-fighting treatments which has excited scientists, doctors and the public all over the world.

Structure of Teixobactin- A novel antibiotic
Structure of Teixobactin- A novel antibiotic

Teixobactin is an extract of β-proteobacteria named Eleftheria terrae. This antibiotic is only tested in mice, to become a drug to treat infections in people, clinical trials will need to be carried out to make sure that the drug is safe and works in patients. Human trials are not yet started so the drug will not be available in the market for at least 3-4 years.

Time will prove Teixobactin will develop into a new drug or not.

How Teixobactin was discovered?

A new tool called iChip, was used for the isolation of teixobactin from a soil microorganism Eleftheria terrae which does not grow in test tube in laboratory condition.  This tool or device allow the researchers to dilute the bacteria containing soil samples, sandwich them between two semi-permeable membranes, then immerse them in soil, allowing the bacteria to be grown in the lab in natural condition.

Use of iChip device to extract Teixobactin compound from soil
Use of iChip device to extract Teixobactin compound from soil

Scientists believe that this screening could be a ‘game changer’ for discovering new antibiotics from environmental sources,  as it allows compounds to be isolated from micro-organisms in the soil that do not grow under normal laboratory conditions.

Uses

Teixobactin is not a panacea against all bacteria. According to the researcher, Teixobactin was ineffective against most Gram-negative bacteria but had shown excellent activity against Gram-positive pathogens, including drug-resistant strains:

  1. Potency against most species, including difficult-to-treat enterococci and M. tuberculosis
  2. Teixobactin was exceptionally active against Clostridioides difficile (also known as Clostridium difficile) and Bacillus anthracis.
  3. Teixobactin had excellent bactericidal activity against S. aureus, MRSA (Methicillin-Resistant Staphylococcus aureus), and Vancomycin Intermediate Staphylococcus aureus (VISA)

Mechanism of Action

Mechanism of action of teixobactin
Model for the mechanism of action of teixobactin: lipid II, the precursor of peptidoglycan, is synthesized in the cytoplasm and flipped to the surface of the inner membrane by MurJ or FtsW; lipid III, a precursor of wall teichoic acid (WTA), is similarly formed inside the cell and WTA lipid-bound precursors are translocated across the cytoplasmic membrane by the ABC-transporter TarGH. Teixobactin (TEIX) forms a stoichiometric complex with cell wall precursors, lipid II and lipid III. Abduction of these building blocks simultaneously interrupts peptidoglycan (right), WTA (left) biosynthesis as well as precursor recycling. Binding to multiple targets within the cell wall pathways obstructs the formation of a functional cell envelope. The producer of teixobactin is a gram-negative bacterium that is protected from this compound by exporting it outside of its outer membrane permeability barrier; the target gram-positive organisms do not have an outer membrane. CM – cytoplasmic membrane; CW – cell wall; OM – outer membrane; LTA – lipoteichoic acid; WTA – wall teichoic acid. Image credit: Losee L. Ling et al.

Teixobactin is an unusual depsipeptide that contains enduracididine, methylphenylalanine, and four D-amino acids. It inhibits cell wall synthesis by binding to a highly conserved motif of lipid II (precursor of peptidoglycan) and lipid III (precursor of cell wall teichoic acid).

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Acharya Tankeshwar

Hello, thank you for visiting my blog. I am Tankeshwar Acharya. Blogging is my passion. As an asst. professor, I am teaching microbiology and immunology to medical and nursing students at PAHS, Nepal. I have been working as a microbiologist at Patan hospital for more than 10 years.

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