Antimicrobial peptides from maggots
Insect immunity research will help create new antibiotics
The staff of the Laboratory of Biopharmacology and Immunology of Insects of St. Petersburg State University proposed a new approach to solving the problem of drug resistance of bacterial pathogens. Scientists have investigated the mechanism of antibacterial immunity of insects and created a drug containing a complex of antimicrobial peptides. This drug is effective against antibiotic–resistant biofilms - the most common form of bacterial infections in humans and animals. Results of the research supported by the grant Published in the journal PLoS ONE (Gordya et al., Natural antimicrobial peptide complexes in the fighting of antibiotic resistant biofilms: Calliphora vicina medicinal maggots).
The discovery of antibiotics in the first half of the 20th century radically improved the treatment of bacterial infections, which previously served as the main cause of death. However, since then, the effectiveness of antibiotics has been constantly decreasing, and now medicine has entered a period that is called the "end of the era of antibiotics". Two of the most important aspects of this problem can be distinguished: the widespread spread of antibiotic-resistant forms of bacteria under the pressure of natural selection and the formation of biofilms (multicellular communities of bacteria attached to the surfaces of human organs and immersed in a protective matrix).
Unlike antibiotic-sensitive free-living counterparts, the inhabitants of biofilms have a natural resistance to antibiotics. Biofilms cause about 80% of bacterial diseases, including intractable chronic infections and related inflammatory, autoimmune and oncological diseases, lesions of almost any organs. The appearance of antibiotic-resistant (immune) bacteria, most of which also form biofilms, adds to the severity of this problem.
The staff of St. Petersburg State University offers a new approach to the destruction of pathogenic biofilms. "The idea underlying our work came from a seemingly distant field of biology from medicine – insect immunology. Studying the mechanisms of antibacterial immunity of insects, we drew attention to the fact that insects, in response to infection with bacteria, synthesize and accumulate a complex set of antimicrobial peptides in the hemolymph (an analogue of human blood)," commented the head of the study, Doctor of Biological Sciences Sergey Chernysh.
As a model for the study, the researchers chose the larvae of meat flies of the family Calliphoridae, living in an environment maximally contaminated with pathogenic microflora for humans. It turned out that the antibacterial protection of these insects includes a combination of dozens of antimicrobial peptides of four families (defensins, cecropins, diptericins, proline-rich peptides), is configured to fight specifically against human pathogens characteristic of their habitat (enterobacteria, staphylococci, etc.) and differs in at least one unique feature: many bacteria do not able to acquire resistance to the complex of these peptides in conditions in which they quickly become resistant to conventional antibiotics.
According to Sergey Chernysh, an attempt to create a combination of synthetic peptides that mimic the properties of a natural composition will be doomed to failure, since modern research methods allow us to develop binary (maximum, triple) combinations, but not combinations of dozens of compounds. The production of such drugs by chemical and genetic engineering synthesis methods will be technically and economically unworkable.
"To solve this problem, we have developed and used a fundamentally different approach. We can call it a parallel biosynthesis technology, in which the entire necessary set of peptides is synthesized by the cells of the insect immune system and is purified while preserving the composition and ratio of natural antimicrobial peptides," says the head of the grant.
Studies have shown that the drug obtained in this way effectively destroys antibiotic-resistant biofilms of various types. Experiments on model biofilms have shown that the drug is promising for the treatment of the most common infections caused by enterobacteria, staphylococci, Acinetobacter and, probably, many other pathogens of intractable (or currently incurable) diseases.
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28.04.2017