According to a new study, a small molecule like a bond can be a powerful tool in the fight against infectious diseases. Nature In Co -Authoría of Researchers at the University of Illinois in Chicago.
Lariocidine, a peptide made by bacteria living on the ground, was effective against several different microbes responsible for mortal infections. The UIC researchers who work with collaborators at the McMaster University in Canada determined how the new antibiotic works and why the medicine evades bacterial resistance.
“The Holy Grail in the field is to find an antibiotic that joins a new objective of the site, has a new mechanism of action and has a new structure, compared to the antibiotics that have been known before,” said Alexander Mankin, distinguished professor of pharmaceutical sciences at UICs. “Lariocidine reaches all these objectives.”
The document was co-author by the postdoctoral researcher of UIC Dmitrii Travin and includes the co-authors of the UIC Mankin, Elena Aleksandrova, Dorota Klepacki, Nora Vázquez-Laslop and Yury Polikanov.
Lariocidine is a newly discovered member of the Lazo peptides family: small proteins formed as a loop, with an amino acid loop at one end and a threaded tail through it. The new peptide was discovered in bacteria collected in the backyard of one of Canada’s scientists.
After McMaster researchers observed that lariocidine could kill several microbes that cause disease, worked with the UIC researchers to study how it works. In biochemical and structural experiments, the team discovered that lariocidine joins and blocks ribosome, the cell factory to make new proteins.
“We found a new job for these loop peptides,” said Travin. “No one knew that Lasso peptides could join Ribosome and kill bacteria by not allowing them to make new proteins.”
Because lariocidine joins a different site from where other antibiotics bind to ribosomes, avoid the defenses that bacteria have evolved to resist other medications.
“In the field of antibiotic discovery, you want a weapon that kills by attacking something different from the previous ones they did before,” said Polikanov, associate professor of biological sciences. “Otherwise, the previously used protections will automatically lead to the defense against the new molecule.”
The unique structure of the peptide can also help avoid another common bacterial defense, said Travin. To tie a ribosome, an antibiotic first needs to enter the bacterial cell. Many drugs collide in transporters, but bacteria can change or eliminate them to block drugs.
On the contrary, lariocidine has a strong positive load, which probably allows it to pass directly through the membranes without the need for transporters. That makes the molecule a broad spectrum antibiotic.
“If you don’t trust any specific transporter, most bacteria can penetrate,” said Travin. “And if a transporter is not needed, then the probability of resistance is lower.”
The researchers also studied a variant of lariocidine, which acquires a more intricate three -dimensional form, rolling their tail to resemble a pretzel. This even more stable structure could be the most promising candidate for clinical development, researchers said. The bioinformatic analysis of the available bacterial genomes suggests that there could be other peptides of Llosso and Pretzel that are directed to the ribosomes that must still be discovered in nature.
“Essentially, lariocidine is the founding member of a new family of antibiotics with a similar mechanism of action,” said Travin. “Time will show if other peptides of this type will be even more active than this. But we already have our foot on the door.”
Research financing was provided by National Health Institutes to Polikanov, Mankin and Vázquez-Lap.
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