Defensins will help antibiotics
Antimicrobial peptides of humans have been proposed to be used together with antibiotics for the treatment of bacterial infections
RNF Press Service
Scientists have studied human antimicrobial peptides, their amount necessary to destroy the causative agent of the disease, and the degree of influence on certain bacteria. Based on the results, a new strategy was proposed to combat pathogenic bacteria resistant to antibiotics. In the future, such studies will help to create new antimicrobial drugs and treatment methods based on the use of antimicrobial peptides.
The results of the study, conducted with the support of the Presidential Program of the Russian Science Foundation (RNF), are published in the journal PeerJ (Albert Bolatchiev, Antibacterial activity of human defensins against Staphylococcus aureus and Escherichia coli).
According to WHO, antibiotic resistance is one of the most serious threats to human health, food security and development. More and more bacterial infectious diseases – for example, pneumonia, tuberculosis, gonorrhea and salmonellosis – are becoming more difficult to treat due to the reduced effectiveness of antibiotics.
"The fight against bacteria that are not sensitive to modern drugs is very important. This is due, firstly, to the growing mortality rate - every year more than 700 thousand people die from antibiotic–resistant infections, by the middle of the XXI century this figure will reach 10 million deaths every year. Secondly, antibiotic–resistant bacteria cause enormous economic damage to the healthcare system - patients with such infections stay in the hospital much longer, they have a higher risk of death, a higher risk of side effects due to the duration of treatment. It is obvious that we need a fundamentally new approach to the fight against antibiotic–resistant pathogens," notes Albert Bolatchiev, project manager for the RNF grant, Candidate of Medical Sciences, employee of Stavropol State Medical University (Stavropol).
One of the types of antimicrobial drugs of the future is antimicrobial peptides. These are fragments of proteins that living organisms produce to fight various infections. An employee of Stavropol State Medical University investigated how antimicrobial human peptides defensins, namely HNP-1, hBD-1 and hBD-3, fight microbes. These peptides were chosen as the most promising, because they act on a variety of microorganisms (bacteria, viruses, fungi).
Although other scientists had previously conducted studies of these peptides, the specific figures remained unclear. For example, what is the minimum amount of medication needed to destroy a specific pathogen – Staphylococcus aureus or E. coli, or what fractional concentration is necessary to combat a large number of bacteria with varying degrees of antibiotic resistance.
The antimicrobial effect of defensins was investigated by the author of the article against 27 strains of Staphylococcus aureus and 24 strains of E. coli – in total, more than 50 different strains of these pathogens were analyzed. In order to test the "strength" of the antibacterial action of defensins (as well as their combination with antibiotics), a standard method of serial dilutions, the so-called "chessboard" method, was used. The simplicity and convenience of the method is that you can visually see what concentration of the substance is necessary to suppress the growth of bacterial colonies. In addition, the use of the technique makes it possible to evaluate the combined antimicrobial effect of two substances on bacterial pathogens.
"The simplicity and convenience of the method lies in the fact that everything is visible to the eye. The study itself takes 48 hours. Of course, there are also difficulties – you need a lot of different bacterial strains, that is, bacteria of the same species, but with different properties and with different sensitivity to antibiotics. The more different strains there are, the higher the accuracy of the experiment," the researcher explains.
So, the scientist managed to show that if you combine antibacterial drugs, for example, rifampicin and amikacin together with defensins HNP-1 or hBD-3, then you can reduce the number of the first several times. This means that in the future we will be able to "restore" a new life to antibiotics that have lost their effectiveness. In addition, it turned out that the antibiotics to which a particular bacterium is resistant (the phenotype of antibiotic resistance) does not affect the sensitivity of the studied bacteria to antimicrobial peptides in any way. Thus, for antimicrobial peptides (defensins), it does not matter how strong the bacteria are against conventional antibiotics – defensins destroy any pathogens with equal force.
"The most interesting thing we found out is that even if the bacterium is very resistant to various antibiotics, it still dies when exposed to antimicrobial peptides," Albert Bolatchiev emphasizes.
According to the scientist, the data obtained can be used to find and develop new strategies for overcoming resistance to antimicrobial drugs used in clinical practice.
"One of the ways to use and introduce antimicrobial peptides into medicine is to find ways to launch the synthesis of a person's own peptides in combination with the introduction of "conventional" antibiotics. This strategy, on the one hand, can ensure the overcoming of resistance to antibacterial drugs, and on the other hand, will give an inexpensive method of therapy. The introduction of defensins into the body from the outside is expensive, since the synthesis of peptides today is a rather expensive technology. We want to make sure in the future that our body produces these defensins by itself," Albert Bolatchiev argues.
Today there are still many unresolved issues that do not allow testing defensins for the treatment of human infections.
"Firstly, these are very expensive molecules. Secondly, they are rapidly destroyed, and they need a lot. Thirdly, there are limitations associated with their toxicity in high doses. Scientists are considering several solutions to these problems. So, it is possible to administer low doses of defensins in combination with conventional antibiotics, which we have shown. In addition, we can find ways to stimulate the synthesis of our own defensins – we can force our body to produce more peptides. It would also be possible to develop new – short and cheap in production – modified defensins. Just in further studies, I plan to test these assumptions," the researcher concludes.
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