Breast milk albumins increase the susceptibility of bacteria to antibiotics
Hamlet from breast milk defeats bacteria
The international team of scientists working on the project included Russian researcher Boris Zhivotovsky and American Anders Hakansson.
Scientists isolated alpha-lactalbumin from female breast milk to investigate how the drug affects the ability of bacteria to penetrate human cells. A cancer cell line was chosen as a test system. What was the surprise when it turned out that the isolated protein complex demonstrated not only antibacterial activity, but also the ability to selectively kill cancer cells, leaving healthy cells unharmed.
Since then, the study of HAMLET properties has developed in two directions. In the laboratory of Anders Hakansson, at the Department of Microbiology and Immunology of the University of Buffalo, USA, they continued to study the antibacterial properties of Hamlet. In August 2012, an article by The Human Milk Protein-Lipid Complex HAMLET Sensitizes Bacterial Pathogens to Traditional Antimicrobial Agents appeared in the journal PLoS ONE about the effectiveness of using this drug against one of the pathogens of pneumonia – Streptococcus pneumoniae. Moreover, not a simple microbe, but one that has developed resistance to penicillin (PRSP) in the process of fighting for its existence.
Now these results are supported by new studies in which HAMLET demonstrated its bactericidal abilities in the fight against methicillin-resistant Staphylococcus aureus (MRSA). A new article by Anders Hakansson, co–authored with his collaborators Laura Marks and Emily Clementi – Sensitization of Staphylococcus aureus to Methicillin and Other Antibiotics In Vitro and In Vivo in the Presence of HAMLET - appeared in PLoS ONE on May 1, 2013. The HAMLET drug for research was provided by Katarina Svanborg.
Scientists from the University of Buffalo have found out that the HAMLET protein complex obtained from mother's milk returns the susceptibility of bacteria to "old" antibiotics, such as penicillin, erythromycin.
The effect of the drug has been demonstrated both in a Petri dish and in animal experiments. In Petri dishes, the drug destroyed bacterial biofilms and colonies of microorganisms, and in experiments on mice, it killed bacteria that infected rodents through the respiratory tract (intranasally).
The effect was so strong that bacteria, including those responsible for persistent nosocomial infections that are not treatable and often lead to the death of patients, "remembered" that they were supposed to die from antibiotics. "It has become possible to reduce the concentrations of antibiotics used in the fight against infections. In addition, HAMLET will allow us to return to the use of conventional antibiotics against resistant strains," Anders Hakansson believes.
It seems that the bacteria cannot acquire resistance to the HAMLET drug, they continue to die in huge quantities and for a long time after its exposure. In the laboratory of Katarina Svanborg at Lund University in 1995, the mechanism of action of the drug (Apoptosis induced by a human milk protein) was investigated.
At the same time, it was shown that in some bacteria (including S.pneumoniae and S.aureus), HAMLET damages the ion transport system into and out of the cell. It also blocks the activity of two enzymes that provide a key biochemical process – glycolysis. As a result, the energy supply system of the bacterial cell is disrupted, and it dies.
HAMLET triggers a cascade of biochemical reactions similar to those in apoptosis, when microbes turn on a self-destruction program "for the benefit of the entire bacterial community." In nature, such a scenario is realized during the formation of biofilms – special microbial communities. This process begins with an increased intake of calcium into the cell and activation of the serine/threonine kinase enzyme, and ends with the rupture of cell membranes and the death of the microbe.
"Unlike synthetic drugs, HAMLET is a natural complex of milk albumin and lipids. And therefore it does not cause side toxic reactions, which we so often observe in cases when we have to use powerful antibiotics to eradicate drug–resistant microorganisms," Laura Marks, a graduate student at the University of Buffalo School of Medicine and Biomedical Sciences, sees the benefits of the drug. The idea to test how HAMLET will work in combination with antibiotics came to Laura Marks's mind when she got acquainted with the results of a study that used a "cocktail" of drugs for the treatment of HIV. "What really attracted me to this work was the idea of a drug combination, where each drug with its own mechanism can enhance the effect of other drugs," explained Laura Marks. "It was curious to find out whether HAMLET would show a synergistic interaction with traditional medicines."
In laboratory experiments, HAMLET helped reduce the dosage of antibiotics needed to fight Pneumococcus and Staphylococcus aureus by eight times or more. The effect was so strong that resistant "superbugs", including a strain of Staphylococcus aureus, insensitive to vancomycin, the "antibiotic of last resort", became vulnerable again.
As a result, the Department of Science and Technology at the University of Buffalo filed a preliminary application for a patent for the use of HAMLET against bacteria, and Anders Hakansson and his wife Hazelin founded a company called Evincor to further promote their developments.
"Currently, the pharmaceutical industry is reluctant to develop the direction associated with obtaining new generations of antibiotics, because they can be used for a short time, infrequently and only in cases when other drugs are ineffective," explained Hazelin Hakansson. – On the other hand, HAMLET should most likely be attributed to adjuvant (enhancing) drugs. It can be widely used in combination with conventional antibiotics. It has a huge "market" potential for the next couple of years, since the immunity of microorganisms to antibiotics is constantly growing."
Some experts believe that the moment when we exhaust all the possibilities of antibiotics in the fight against microbes is not far off. And, probably, this is another reason to recall the brilliant dictum of Winston Churchill: "The best investment is the investment of milk in a child."
Portal "Eternal youth" http://vechnayamolodost.ru06.05.2013