Health systems worldwide are increasingly losing the battle against multidrug-resistant bacteria. New antibiotics are scarcely developed before they become unusable. Now researchers have discovered special lipids that can boost the immune system to combat multidrug-resistant infections. The method can possibly be reused in future cancer treatment.
When bacteria attack humans, the body’s frontline of defence is various cells that recognize and attack the enemy. In response, some bacteria have developed methods of weakening the line of defence by doing such things as preventing the body from producing fatty substances – lipids – that are essential for keeping the immune system active.
An Italian-Danish research collaboration has now revealed that feeding the immune system’s phagocytes with bioactive lipids can strengthen the immune response in the fight against multidrug-resistant bacteria. The researchers exploited the fact that the phagocytes consume and digest invasive particles.
“By feeding them with liposomes filled with the bioactive lipids, we can make them stronger and more effective. Our latest results show that this is sufficient to restore the immune system’s ability to combat even multidrug-resistant tuberculosis infections,” explains Maurizio Fraziano, Professor at the Department of Biology of the University of Rome Tor “Vergata”.
Tricking the immune system to take medicine
There is nothing new about the fact that bioactive lipids can help to strengthen the immune system in fighting invasive organisms. The really cunning thing about this new system is how the researchers were able to sneak the new lipid medicine in. Lipids on their own never reach the immune system’s cells, so the researchers therefore had to develop special vehicles for the lipids.
“The lipids are encased in liposomes – small round beads. These enable the bioactive lipids to be transported throughout the body. We covered the outside with phosphatidylserine, which led to them being recognized and consumed by the phagocytes. This technique ensures that the lipids arrive at the required location.”
Phosphatidylserine is usually located on the inside surface of cell membrane by the activity of enzyme flippase. When one of the body’s cells needs to be destroyed, some of the phosphatidylserine molecules move to the surface of the cell, signalling to the phagocytes that they can feed on the dying cell. This is called apoptosis – programmed cell death.
“In this situation, the phagocytes are fooled into believing that the liposomes are the cells that should die and need to be eaten. Thus, they consume the lipids that make them more effective in combating bacteria. The important new aspect of this study is that we show that we can induce phagocytes that are weakened for a variety of reasons to regain their strength and thereby combat infections. The decisive new feature is that we can make this work in practice against lung infections that no longer respond to ordinary drugs.”
Falling between two stools
Nevertheless, it is too early to get excited about these new miracle lipids. The Italian researchers have not yet been able to find investors willing to fund the further testing and development of the new method.
“The problem is presumably that our method falls between two stools. This is neither a vaccine against bacteria nor a new antibiotic. The method does not therefore immediately fit into the established treatment system or the existing drug industry.”
Francesco Cecconi, co-author of the article, is a professor and head of the Cell Stress and Survival research unit of the Danish Cancer Society Research Center. He is very optimistic about applying the new results in combating both multidrug-resistant bacteria and potentially cancer.
“We are continually researching the cellular life processes to understand the complex mechanisms that control the development of cancer cells and why, for example, they do not die even when something is wrong with them. This makes the new system with bioactive lipids extremely interesting, because the lipids may activate various enzymes that can induce cancer cells to be programmed to die anyway.”
Maurizio Fraziano and Francesco Cecconi are now testing the new method in future cancer research.
“Similar to bacterial infections, macrophages in cancer are a decisive factor because these must ultimately recognize and destroy the cancer cells. The new system therefore has enormous potential, and we are optimistic that the method may also work in cancer treatment,” concludes Francesco Cecconi.
“Liposomes loaded with bioactive lipids enhance antibacterial innate immunity irrespective of drug resistance” has been published in Scientific Reports. In 2016, the Novo Nordisk Foundation awarded a grant to Francesco Cecconi for the project The Autophagy Regulator Ambra1 and Lung Cancer: a Novel Prognostic Biomarker and Therapeutic Target.