Scientists have discovered a completely new way to cut the legs out from under drug-resistant bacterial infections.
A new class of antibiotics has been identified by researchers at Uppsala University in Sweden, and although it has only been tested in mice, the research team hope Further development of the drug “could make an important contribution to the continued fight against antibiotic resistance,” he said.
something like a unique medicine many other antibiotics Currently under development, it targets the double membrane that surrounds Gram-negative bacteria. Escherichia coli, Can cause intestinal and blood infections Klebsiella pneumoniae, It can cause lung, bladder, and blood infections.
Unlike Gram-positive bacteria, for which numerous families of drugs are made, a formidable secondary barrier surrounding the cells of Gram-negative bacteria makes antibiotics more difficult to work with.
The strong adventitia has lipopolysaccharideprovides integrity to the cell, allows the cell to interact with other surfaces, allows for the expulsion of toxins and the entry of nutrients.
For years, scientists have been trying to tinker with the very lipid membranes that are essential to the function of Gram-negative bacteria. But for the first time, Swedish researchers targeted an enzyme called LpxH, which helps synthesize another important component of the outer membrane called lipopolysaccharide. Approximately 70% of Gram-negative bacteria utilize this enzyme, making it a potentially good target for many infectious diseases.
Mice injected with drug-resistant substances Escherichia coli or Klebsiella pneumoniae One hour later, a series of compounds designed to inhibit bacterial LpxH were administered. The results demonstrated that just one dose can treat bloodstream infections in just four hours.
“During this infection model, the bacteria spread to the bloodstream of the mice,” they said. explain.
“The ability of these compounds to significantly reduce the number of bacteria recovered from blood after just one dose highlights their potential to treat the most life-threatening Gram-negative infections. [multi drug resistant] Pathogens. ”
The researchers started with a compound called JEDI-1444, which they gleaned from a literature search for suitable inhibitor candidates. Although it showed incredible promise in preventing the growth of Gram-negative bacteria, its solubility and stability in blood were not very high.
After some modifications, the team found success with two variants coded EBL-3599 and EBL-3647. Although these did not have good solubility in serum, they showed the following results.Effective“Broad-spectrum antibacterial action” Escherichia coli and Klebsiella pneumoniae are isolated “regardless of resistance genotype.”
This is an important discovery given that both of these bacteria are becoming increasingly resistant to some of the available antibiotics that act on them. In 2019, deaths from antibiotic-resistant infections were the third leading cause of death worldwide. By 2050, 10 million people are expected to die annually.
As bacteria adapt to our drugs, new classes of drugs are desperately needed to save lives. Half of the antibiotics available on the market today are simply variations of drugs identified nearly a century ago.
World Health Organization (WHO) in 2017 released At the top of the list are Gram-negative bacteria, which are resistant to the most dangerous drug-resistant pathogens and the most effective types of broad-spectrum antibiotics.This too Escherichia coli and Klebsiella pneumoniae, Pseudomonas aeruginosa, It can also cause pneumonia Acinetobacter baumannii, It causes blood, lung, and urine infections.
“The current results are very promising,” say the Uppsala researchers. conclude“Significant additional work will be required before this class of compounds can be used in clinical trials.”
This study PNAS.
