Wasp venom against bacteria
Based on the results of a systematic study of the antimicrobial properties of a toxin that is part of the venom of the South American wasp, researchers at the Massachusetts Institute of Technology have developed several variants of a peptide that has a powerful antimicrobial effect and is harmless to human cells.
The immune system of all organisms, including humans, produces peptides capable of destroying bacteria. In search of a solution to the problem of antibiotic-resistant bacteria, many researchers are trying to adapt such peptides for use in medicine.
Many compounds with antibacterial properties are found in the venom of insects, such as wasps and bees. However, unfortunately, many of these substances are toxic to humans, which makes them unsuitable for use as antibacterial drugs.
The authors turned their attention to one of the peptides contained in the venom of the South American wasp Polybia paulista, which have an antibacterial effect. According to one of the leaders of the work, Dr. Cesar de la Fuente-Nunez, the small size of the molecule of this peptide - only 12 amino acids – made it possible to modify the maximum possible amount of amino acid residues to determine the contribution of each of the components of the molecule to its antimicrobial activity and toxicity. Like most other antimicrobial peptides, the selected compound kills bacteria by destroying their cell membranes. The interaction of the peptide with bacterial cell membranes is provided by the single-chiral structure of its molecule.
At the first stage of the work, the researchers created several dozen modifications of the original peptide, after which they evaluated the effect of the changes on the helical structure and hydrophobicity of the peptides, which also affects their interaction with cell membranes. After that, the peptides were tested on seven strains of bacteria and two strains of fungi, which allowed us to calculate the correlation between their structure, as well as physicochemical properties and antimicrobial activity.
Based on the identified structural and functional relationships, several dozen more peptides were constructed for further testing, which made it possible to establish the optimal ratio of the number of hydrophobic amino acids and positively charged amino acids. In addition, a cluster of amino acids has been identified, any changes to which disrupt the overall functionality of the molecule.
The toxicity of peptides was evaluated on human embryonic kidney cell culture. The most promising molecules were selected for experiments on mice infected with a strain of Pseudomonas aeruginosa bacteria resistant to traditional antibiotics, which cause serious infections of the respiratory and urinary tracts. Some of the tested peptides suppressed the course of infection, while one of them in a high dose for 4 days completely freed the animals from bacteria.
Currently, the authors are working on creating additional variants of peptides in the hope that they will be able to cope with infection in lower doses. In addition, Fuente-Nunez plans to apply the developed approach to other types of natural peptides with antimicrobial properties.
Article by Marcelo D. T. Torres et al. Structure-function-guided exploration of the antimicrobial peptide polybia-CP identifies activity determinants and generates synthetic therapeutic candidates is published in the journal Nature Communications Biology.
Evgenia Ryabtseva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of the Massachusetts Institute of Technology: MIT engineers repurpose wasp venom as an antibiotic drug.