Researchers at the University of Illinois at Chicago have found that a natural peptide from fruit flies, called drosocin, can bind to bacterial ribosomes and inhibit protein production, forcing the bacterial cell to self-destruct. These findings, together with an understanding of their mechanism of action, could facilitate the creation of new antibiotics.
A new study demonstrates the antibacterial mechanism of peptides.
Researchers from the University of Illinois at Chicago have found that peptides derived from fruit flies could pave the way for the development of new antibiotics.
Posted in Chemical Natural BiologyTheir study revealed that a naturally occurring peptide, known as drosocin, protects insects from bacterial infection by binding to bacterial ribosomes. Once bound, Drosocin prevents the ribosome from properly completing its primary job – making new proteins, which the cell needs to function.
Protein production can be stopped by disrupting various stages of translation – the process by which DNA is “translated” into protein molecules. UIC scientists found that drosocin binds to the ribosome and prevents translation termination when the ribosome hits a stop signal at the end of the gene.
“Drosocin is the second peptide antibiotic known to stop translation termination,” said Alexander Mankin, study author and Distinguished Professor of the Center for Biomolecular Sciences and the Department of Pharmaceutical Sciences at the Faculty of Pharmacy. The other, called apidaecin and found in honey bees, was first described by UIC scientists in 2017.
The UIC laboratory, co-led by Mankin and Nora Vázquez-Laslop, a research professor at the Faculty of Pharmacy, has been able to produce fruit fly peptides and hundreds of their mutants directly in bacterial cells.
“Drosocin and its active mutants that are made in bacteria force the bacterial cell to self-destruct,” says Mankin.
While the peptides drosocin and apidaecin act in a similar way, the researchers found that their chemical structure and the way they attach to the ribosome are different.
“By understanding how these peptides work, we hope to exploit the same mechanism for potential new antibiotics. Side-by-side comparison of peptide components facilitates the engineering of new antibiotics that take the best out of each,” said Mankin.
Reference: “Inhibition of translation termination by the antimicrobial peptide Drosocin” by Kyle Mangano, Dorota Klipaki, Erosa Ohanmo, Chitana Palega, Weiping Huang, Alexandra Brakel, Andor Krisan, Yuri S. Polikanov, Ralph Hofmann, and Nora Vazquez-Laslope 23. Chemical Natural Biology.
DOI: 10.1038/s41589-023-01300-x
This study was funded by the National Institutes of Health.
2023-07-23 17:02:47
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