The substitutes are based on a combination of amino acids and fatty acids
Technion researchers have found a new way to produce effective substitutes for antibiotics, based on a combination of amino acids and fatty acids. The bacteria are not able to develop resistance against these substitutes, thus their great advantage.
Professor Amram Mor and students from his research team, Keren Marinka and Shahar Rotem from the Faculty of Biotechnology and Food Engineering, found a way to preserve peptides in the body, which are tiny proteins found in every organism and are part of the human immune system. They last only a short time in the body, usually lasting up to a few minutes. The Technion researchers' success in stabilizing them and keeping them in the body for hours thanks to a unique structure, makes them an effective medicine.
"We found a way to shorten the natural molecule and thus reduce its production, and at the same time - to optimize it so that it successfully fights against bacteria and pests," explains Professor Moore. "With the help of Professor Uri Kogan and Dr. Irina Fortnia from our faculty, we added a fatty acid to the short molecule, and the activity improved even more. We can also decide which bacteria we want to attack with the help of the peptides."
In an article recently published in the prestigious scientific journal Chemistry & Biology, Technion researchers show how, with the help of fatty acid, they make the peptide specifically active against the bacterium "Pseudomonas", which usually causes lung diseases. It is important that the peptide acts specifically against the bacteria, so as not to harm healthy body cells or even neighboring bacteria that belong to the natural microflora during the treatment. The result of the research is a peptide-like substance, which did succeed in breaking down the pathogenic bacterium (a disease-causing bacterium).
"It is, in fact, about building specific selectivity against traditional pathogenic bacteria, and increasing the effectiveness of the treatment while significantly reducing toxicity and side effects," the Technion researchers explain.
Professor Moore has been researching peptides for about twenty years. During his research he isolated a group of peptides, which were taken from monkey frogs (frogs that live on trees). He tested the effectiveness of the peptides against antibiotic substances, and found that the effectiveness of the peptides did not decrease at all over time, while the effectiveness of the antibiotics did decrease since the bacteria are able to develop resistance against the antibiotics. He showed that in order to preserve the effectiveness of an antibiotic substance, its dose must be increased a hundred times from the original dose, while in order to preserve the effectiveness of the peptide-like substance there is no need to increase its dose.
Uniting forces
Weizmann Institute scientists have developed a method to produce effective drugs against antibiotic-resistant bacteria and fungi
Bacteria and fungi that have developed resistance against various antibiotic drugs are considered one of the most prominent threats to human health in the current century. A group of scientists from the Weizmann Institute of Science, led by Prof. Yehiel Shay from the Department of Biological Chemistry, recently developed an original and powerful way to deal with this threat. The new method developed by the scientists is based on a combination of two types of weapons capable of harming bacteria and fungi and making it difficult for them to develop resistance against them.
Normal antibiotic drugs attack various components that carry out vital actions inside the bacterial or fungal cell. Thus they harm the causes of the diseases but do not cause them mechanical damage. As a result, the damaged bacteria and fungi manage to pass on to their future generations information about the drug that harmed them, thus allowing them to develop a better defensive ability, which sometimes goes as far as developing resistance against the drug.
The idea is based on studies showing that different organisms have weapons that allow them to deal with the microbial threat. These are two types of weapons that destroy the membrane of the bacterium or fungus and thus destroy the enemy at a speed that does not allow him to learn the characteristics of the weapon, so that he cannot transmit information to future generations, which prevents the development of resistance against this weapon. The problem is that most of these weapons are complex in structure, work on limited strains of bacteria or fungi, and are difficult to harness for medical use. The scientists of the institute, Prof. Yehiel Shay and research students Eric Makowitzki and Dorit Abrahami, developed a method to combine these two types of weapons and create a combined weapon that may serve as a basis for developing drugs against bacteria and fungi that are resistant to antibiotics. The findings of their research were recently published in the scientific journal "Records of the American Academy of Sciences" - PNAS.
One type of weapon is the antimicrobial peptides (AMP), which are made of amino acids that give them a positive electrical charge. This feature allows them to stick like a magnet to the membranes of bacteria that carry a negative electrical charge. Another kind of weapons are lipo-peptides built from fatty acids and amino acids that give them a negative electrical charge, which allows them to generally act against fungi. In fact, the property that allows lipo-peptides to work effectively against the fungi is the fact that they are hydrophobic - "haters water".
Prof. Shi and his students succeeded in imitating nature and designing synthetic lipo-peptides characterized by the two key properties - a positive electric charge, and the hydrophobicity derived from different fatty acids. In fact, they have created a number of combination weapons, some of which work against both bacteria and fungi, and some of which are directed against only fungi or only against bacteria. In any case, these are very powerful weapons and they are able to damage different strains of the disease agents.
Prof. Shay: "We were surprised to find that these small peptides are just as effective, and sometimes more so, than the natural peptides. It is still necessary to find out exactly how this efficiency is achieved. This research, which began as basic research, may lead, in the future, to the development of many applications. The fact that the peptide is so short makes it particularly attractive for the pharmaceutical industry, as it is easier and cheaper to produce. The fact that it causes mechanical damage to bacteria and fungi makes it difficult for them to develop resistance against it. In addition, it can be designed so that it works against a wide variety of bacteria and fungi."
These new synthetic peptides contain only four amino acids (natural antibacterial peptides contain 12-50 amino acid molecules), yet they are just as effective, and often more so, than the natural peptides. In addition, they are easier and cheaper to produce, and can be designed to act against a wide variety of bacteria and fungi. At this stage, many lipo-peptides are characterized by low toxicity to mammalian cells, which does not allow them to be used for the production of new drugs. Therefore, the next challenge facing the scientists is the need to design them so that they are safe for use in humans. It seems that this design would be possible, since in the process of creating the synthetic lipopeptides, the scientists have already managed to change some of their properties, according to their will.
