Scientists altered a highly toxic protein from a common Asian wasp species, Vespula lewisii. Scientist intervention
It is known that there is an urgent need fornew drugs to treat bacterial infections, as many types of circulating bacteria have developed resistance to old antibiotics. The US Centers for Disease Control and Prevention estimates that nearly three million Americans become infected with antibiotic-resistant microbes each year, causing more than 35,000 deaths. Globally, the problem is even worse. In 2017, sepsis, an often fatal inflammatory syndrome caused by extensive bacterial infection, accounted for about one in five deaths worldwide.
Senior study author Cesar de la Fuente, Ph.D., associate professor in the Department of Psychiatry, Microbiology and Bioengineering in Pennsylvania, described how the study proceeded.
Scientists started with a little protein, orA "peptide" called mastoparan-L, a key ingredient in the venom of the wasp Vespula lewisii. The venom containing mastoparan-L is usually not dangerous in small doses for a person bitten by a wasp, but it is still quite toxic. It destroys red blood cells and induces a type of allergic / inflammatory reaction that can lead to anaphylaxis in susceptible individuals.
Mastoparan-L (mast-L) is also known for itsmoderate toxicity to bacterial species, making it a potential starting point for the development of new antibiotics. But until now, it was not known how to enhance its antibacterial properties and how to make it safe for humans.
The researchers decided to replace a site at one end of the mast-L protein, which is believed to be a major source of toxicity to human cells, and it worked. This is how the scientists obtained the mast-MO peptide.
In a key series of experiments, the researcherstreated mice with the new antimicrobial peptide hours after infecting them with deadly, sepsis-causing strains of E. coli or Staphylococcus aureus bacteria. In each test, the drug saved the life of 80% of the treated mice. Potential toxic side effects with higher doses — doses at which mast-MO did not cause overt toxicity.
De la Fuente and his colleagues found evidence ina study that mast-MO kills bacterial cells by making their outer membranes more porous, which may also improve the ability of co-administered antibiotics to enter cells. At the same time, mast-MO appears to suppress harmful immune overreaction that can lead to severe illness in some bacterial infections.
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