In this news, we discuss the Scientists turn wasp venom toxins into promising antibiotics.
Scientists have engineered powerful new antimicrobial molecules from toxic proteins found in wasp venom. The team at the University of Pennsylvania’s Perelman School of Medicine hope to develop the molecules into new bacteria-killing drugs, a significant breakthrough given the growing number of antibiotic-resistant bacteria that can cause diseases such as sepsis and sepsis. tuberculosis.
In the study, published in the Proceedings of the National Academy of Sciences, researchers modified a small, highly toxic protein from a species of common Asian wasp, Vespula lewisii, the Korean yellowjacket wasp. The modifications improved the molecule’s ability to kill bacterial cells while significantly reducing its ability to harm human cells. In animal models, scientists have shown that this family of new antimicrobial molecules made with these alterations can protect mice against otherwise deadly bacterial infections.
There is an urgent need for new drug treatments for bacterial infections, as many circulating bacterial species have developed resistance to older drugs.
“New antibiotics are urgently needed to treat the ever-increasing number of drug-resistant infections, and venoms are an untapped source of potential new drugs. We believe that venom-derived molecules such as the ones we designed in this study are going to be a valuable source of new antibiotics, ”said study lead author César de la Fuente, Presidential Assistant Professor of Psychiatry, Microbiology and bioengineering at Penn.
De la Fuente and his team started with a small protein, or “peptide,” called mastoparan-L, a key ingredient in Vespula lewisii wasp venom. The venom containing Mastoparan-L is generally not harmful to humans in the small doses delivered by wasp stings, but it is quite toxic. It destroys red blood cells and triggers a type of allergic / inflammatory reaction which in susceptible people can lead to a fatal syndrome called anaphylaxis – in which blood pressure drops and breathing becomes difficult or impossible.
Mastoparan-L (mast-L) is also known for its moderate toxicity to bacterial species, making it a potential starting point for the design of new antibiotics. But there are still some unknowns, including how to improve its antibacterial properties and how to make it safe for humans.
The team searched a database of hundreds of known antimicrobial peptides and found a small region, the so-called pentapeptide motif, which was associated with strong activity against bacteria. The researchers then used this motif to replace a section at one end of mast-L that is believed to be the main source of toxicity to human cells.
In a series of key experiments, researchers treated mice with mast-MO several hours after infecting them with otherwise fatal, sepsis-inducing strains of the bacteria E. coli or Staphylococcus aureus.
In each test, the antimicrobial peptide kept 80 percent of the treated mice alive. In contrast, mice treated with mast-L were less likely to survive and exhibited serious toxic side effects when treated with higher doses – doses at which mast-MO caused no obvious toxicity.
The activity of mast-MO in these tests also appeared comparable to that of existing antibiotics such as gentamicin and imipenem – for which alternatives are necessary due to the spread of resistant bacterial strains.
Researchers created dozens of mast-MO variants and found several that appeared to have dramatically improved antimicrobial potency without toxicity to human cells.
Scientists turn toxins in wasp venom into promising antibiotics
There is an urgent need for new drug treatments for bacterial infections