A new generation antibiotic sets records
In the USA, an antibiotic has been created against antibiotic-resistant infections
Copper news based on the materials of Brown University: Clever chemistry and a new class of antibioticsA joint group of researchers from Brown University and the Massachusetts Institute of Technology improved the structure of acyldepsipeptides (acyldepsipeptides, or ADEP) – substances with antibacterial properties – which made them much more resistant and active in the fight against microorganisms.
According to data published in the Journal of the American Chemical Society (Carney et al., Restriction of the Conformational Dynamics of the Cyclic Acyldepsipeptide Antibiotics Improves Their Antibacterial Activity), modification of these compounds increased their effectiveness a thousand times.
Due to the growth of infections resistant to the action of most antibiotics, scientists are rushing to find new medicines that could replace drugs that are no longer effective. Such a promising class of molecules are some acyldepsipeptides that destroy antibiotic-resistant bacteria, and in a completely different way, different from the mechanism of action of all known antibacterial drugs.
"They bind to a bacterial cell protein that works as a 'cell garbage cleaner,'" said Jason Sello, professor of chemistry and the main author of the work. –This protein, called ClpP, destroys those proteins that are folded incorrectly or damaged, and can be harmful to the cell."
However, when the bacterial protein ClpP binds to the acyldepsipeptide molecule, the protein can no longer act selectively and begins to destroy normal bacterial cell proteins, which eventually leads to its death.
Previous studies have already shown that ADEP is capable of destroying microorganisms that cause staphylococcal infections, certain types of pneumonia, tuberculosis and other infections in in vitro and in vivo experiments (on rats and mice). But inside the acyldepsipeptide molecule there are weak bonds that can be easily broken, so the researchers decided to modify the ADEP molecule in such a way that it becomes more durable. Scientists have managed to synthesize such modified analogues of acyldepsipeptides by changing the location of certain amino acids in them.
In vitro experiments have shown that in comparison with conventional acyldepsipeptides, the compounds obtained by the researchers were much more effective against three pathogenic bacteria: 32 times more effective against Staphylococcus aureus (Staphylococcus aureus), 600 times more effective against fecal enterococcus (Enterococcus faecalis) and 1200 times more effective against Pneumococcus (Streptococcus pneumoniae). In the latter case, as the authors of the work noted, the connection of the synthetic analogue of ADEP with the ClpP protein turned out to be 7 times stronger than usual.
According to the researchers, the increase in antibacterial activity may be due to the fact that the tougher ADEP molecule penetrates more easily through the membrane of a bacterial cell and binds more firmly to its intracellular "cleaner".
Currently, Professor Sello and his colleagues have begun to study the antibiotic effect of modified acyldepsipeptide molecules on mice and to develop a full-fledged antibacterial drug of a new generation based on ADEP.
Portal "Eternal youth" http://vechnayamolodost.ru21.01.2014