Antibiotic resistance is a real public health problem of global dimensions. Finding new antibiotics with a different mode of action from existing antibiotics is very complicated. However, it seems that one team has succeeded in developing a highly original new drug: it is based on existing molecules that have the ability to change their shape! It would have the ability to fight bacteria that are resistant to all currently available antibiotics.
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Multi-Drug Resistant Bacteria. Image Courtesy of Dr Graham Beards
More and more bacteria are becoming resistant to existing antibiotics. It’s a global scourge. While we need to encourage the correct use of antibiotics, we also need to find new molecules with new modes of action to fight bacteria that have become resistant. However, research and development of new drugs, especially in the field of bacteriology, takes a lot of time and money. And it is urgent. One team had a brilliant idea. Instead of designing a new class of antibiotics, they decided to modify existing antibiotics already clinically approved. This would save a lot of time! Their paper was published in the journal PNAS (Proceedings of the National Academy of Sciences).
A molecule that changes shape
The authors designed and synthesized modified vancomycin dimers. Vancomycin, a molecule in the glycopeptide family, is an important antibiotic. It acts by inhibiting peptidoglycan synthesis in the bacterial wall. It is effective against both aerobic and anaerobic Gram-positive bacteria. Modified shapeshifting vancomycin dimers (SVDs) are designed to prevent bacteria from developing resistance. The way these tiny particles change shape is made possible by a special chemical called triazole-linked bullvalene. It helps the particles rearrange their structure in a way that can stop bacteria from building their cell walls. This molecule has the property that it can evolve and change shape. Thus, it can create ligands capable of inhibiting the biosynthesis of bacterial walls.
Very satisfactory antibiotic activity
Experiments have been carried out on wax moth larvae. The vancomycin dimers thus produced have been shown to be effective against several multidrug-resistant bacteria, such as ESKAPE bacteria (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp. ), VRE (vancomycin-resistant enterococci), MRS (methicillin-resistant staphylococci) and VRSA (vancomycin-resistant staphylococci). In principle, the bacteria failed to develop resistance to this new antibiotic.
This re-engineering of existing antibiotics paves the way for new bacteriological research and offers a glimmer of hope in the daunting situation of increasing antibiotic resistance.
FAQ: Shapeshifting Vancomycin Dimers and Antibiotic Resistance
1. What is antibiotic resistance?
Antibiotic resistance occurs when bacteria evolve and no longer respond to existing antibiotics, making infections harder to treat.
2. Why is finding new antibiotics so difficult?
Developing new antibiotics is time-consuming and expensive, requiring years of research to discover new molecules with unique mechanisms of action.
3. How do shapeshifting vancomycin dimers (SVDs) work?
SVDs use a chemical structure called triazole-linked bullvalene, which allows the molecules to change shape and prevent bacteria from building their cell walls.
4. What bacteria are these new antibiotics effective against?
SVDs have shown effectiveness against multidrug-resistant bacteria, including ESKAPE pathogens, vancomycin-resistant enterococci (VRE), methicillin-resistant staphylococci (MRS), and vancomycin-resistant staphylococci (VRSA).
5. Have resistance mechanisms developed against SVDs?
So far, bacteria have not developed resistance to these newly engineered antibiotics, making them a promising alternative.
6. What are the advantages of modifying existing antibiotics?
This approach saves time and resources by building on clinically approved drugs instead of creating entirely new antibiotics from scratch.
7. Have these antibiotics been tested in humans?
Currently, tests have been conducted on wax moth larvae, but further studies are needed before human clinical trials can begin.
8. What does this discovery mean for the future of antibiotic development?
It opens a new path for modifying existing antibiotics, offering hope for combating multidrug-resistant superbugs in the future.
References
Ottonello, A., Wyllie, J. A., Yahiaoui, O., & Moses, J. E. (2023). Shapeshifting bullvalene-linked vancomycin dimers as effective antibiotics against multidrug-resistant gram-positive bacteria. Proceedings of the National Academy of Sciences, 120(15), e2208737120. https://doi.org/10.1073/pnas.2208737120
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