The University of Zurich in collaboration with Spexis has advanced the battle against antibiotic-resistant bacteria by developing a novel class of antibiotics. This breakthrough was achieved by re-engineering the chemical structure of thanatin, a natural peptide. The newly created synthetic peptides exhibit robust effectiveness, safety, and resilience against bacterial immunity in mouse studies, introducing a promising new kind of antibiotic to tackle resistant strains.
There is a significant, urgent need for innovative antibiotics to treat resistant bacteria, as recognized by healthcare professionals globally. The researchers from the University of Zurich and Spexis have transformed the structure of naturally occurring peptides, resulting in antimicrobial agents that interact with novel targets in bacterial metabolism.
With over five million people around the world falling victim to antibiotic-resistant bacteria each year, it is crucial to discover new antibiotics for effective bacterial infection treatment.
Oliver Zerbe, a chemist and the head of the NMR facilities at the University of Zurich, stated, “Regrettably, the pipeline for new antibiotic development is quite bare. It has been over half a century since the last antibiotics targeting new molecules were approved.”
In a recently published study in Science Advances, Zerbe detailed the creation of a highly efficient new class of antibiotics that combat Gram-negative bacteria in a unique manner. This group of bacteria, which the WHO categorizes as highly hazardous due to their double cell membrane enhancing their resistance, includes carbapenem-resistant enterobacteria. Spexis AG researchers were also contributors to the study, which was co-funded by Innosuisse, in a joint effort with the UZH team.
The scientists began their research with thanatin, a peptide that insects utilize to ward off infections. Thanatin interrupts a critical lipopolysaccharide transport bridge between the Gram-negative bacteria’s outer and inner membranes, causing the metabolites to accumulate within the cells, eventually leading to the bacteria’s death. However, due to its low efficiency and the bacteria’s rapid development of resistance against it, thanatin is unsuitable as an antibiotic drug.
As a solution, the researchers chemically modified thanatin to enhance its properties. Zerbe’s team used structural analyses and nuclear magnetic resonance (NMR) to visualize how thanatin binds and disrupts the transport bridge. Spexis AG researchers, armed with this knowledge, planned the necessary chemical modifications to augment the peptide’s antibacterial effects, including further mutations for enhanced stability.
The synthetic peptides were tested on mice with bacterial infections, yielding exceptional results. Zerbe noted, “The new antibiotics showed remarkable effectiveness, particularly in treating lung infections, and against carbapenem-resistant enterobacteria where most other antibiotics fail.” The new peptides also exhibited low toxicity, renal safety, and prolonged stability in blood—qualities essential for drug approval. However, further preclinical trials are necessary before initiating human trials.
The team ensured that the chosen peptides would also be effective against bacteria that have already developed resistance to thanatin. Zerbe expressed confidence that this would greatly decelerate the development of antibacterial resistance. He concluded, “We look forward to the possible emergence of a new class of antibiotics that can also combat resistant bacteria.”
Reference: “Peptidomimetic antibiotics disrupt the lipopolysaccharide transport bridge of drug-resistant Enterobacteriaceae” by Matthias Schuster, Emile Brabet, Kathryn K. Oi, Nicolas Desjonquères, Kerstin Moehle, Karen Le Poupon, Sophie Hell, Stéphane Gable, Virginie Rithié, Séverine Dillinger, Peter Zbinden, Anatol Luther, Claudia Li, Sarah Stiegeler, Carolin D’Arco, Hans Locher, Tobias Remus, Selena DiMaio, Paola Motta, Achim Wach, Françoise Jung, Grégory Upert, Daniel Obrecht, Mohammed Benghezal and Oliver Zerbe, 24 May 2023, Science Advances.
DOI: 10.1126/sciadv.adg3683
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Frequently Asked Questions (FAQs) about Antibiotic-resistant bacteria
What new development has been made in the fight against antibiotic-resistant bacteria?
Researchers at the University of Zurich and Spexis have developed a new class of antibiotics that shows promise in combatting antibiotic-resistant bacteria. They achieved this breakthrough by re-engineering the chemical structure of a natural peptide, thanatin, to produce synthetic peptides that demonstrated effectiveness, safety, and resistance to bacterial immunity in mouse studies.
Who are the main contributors to this research?
The main contributors to this research are a team of scientists from the University of Zurich, including chemist Oliver Zerbe, and researchers from the pharmaceutical company Spexis AG. This research was part of a collaboration co-funded by Innosuisse.
What is the unique mechanism of these new antibiotics?
The new class of antibiotics disrupts a critical lipopolysaccharide transport bridge between the outer and inner membranes of Gram-negative bacteria. This disruption leads to the accumulation of metabolites within the bacterial cells, causing their death.
What were the results of the synthetic peptides in mice tests?
The synthetic peptides yielded exceptional results when tested on mice with bacterial infections. They were particularly effective in treating lung infections and proved highly effective against carbapenem-resistant enterobacteria. The newly developed peptides also exhibited low toxicity, renal safety, and maintained stability in the blood over an extended period.
What are the next steps before these new antibiotics can be tested on humans?
Further preclinical trials are needed before the new antibiotics can begin the first tests in humans. The goal is to ensure the safety and efficacy of the antibiotics before they are used in human trials.
How does this new class of antibiotics help in combating antibiotic resistance?
The researchers ensured that the synthetic peptides would be effective against bacteria that have already developed resistance to thanatin. They are confident that this approach will significantly slow down the development of antibacterial resistance.
More about Antibiotic-resistant bacteria
- University of Zurich Research
- Spexis AG
- Science Advances
- Innosuisse – Swiss Innovation Agency
- Antibiotic Resistance (WHO)
5 comments
this is such important work! resistance to antibiotics is a big problem. hope these new ones are approved for use soon.
As a chemist, I find this fascinating! Using thanatin as a basis for these antibiotics is an ingenious idea. go science!
have been following this research, Zerbe’s team is doing some groundbreaking work. Fingers crossed it goes well.
So we might have a way to combat antibiotic resistance! thats amazing news!! just hope it gets to human trials soon.
Wow, it’s been a long time since I heard any good news about antibiotics… sounds really promising!