Researchers have developed a catalytic antibiotic - which causes cutting and fission of targets in the bacteria - and as a result, its death
The increase in the number of strains of bacteria resistant to antibiotics is a global medical problem that complicates the treatment of infectious and life-threatening diseases. Thousands of people in Israel die every year as a result of infection with such resistant bacteria. One of the sources of the problem is the overuse of antibiotics in recent decades and the difficulty in developing new types of antibiotic drugs.
Bacteria develop resistance to antibiotics due to repeated exposure to it and through the culture and transfer of the DNA segment responsible for resistance. Antibiotic resistance can also pass between bacteria through horizontal genetic transfer - where they acquire genes from the environment or from other organisms; They receive a piece of foreign DNA that can contain up to hundreds of genes that they did not have before, and thus acquire a variety of new traits, including resistance, violence and disease-causing.
What is the question? How can you kill bacteria faster and try to reduce their resistance to antibiotics?
Prof. Timor Bazov from the Technion is a chemist and biochemist who uses synthetic organic chemistry (building new organic molecules) to solve biological problems, including bacterial resistance to antibiotics. In the past, he developed new antibiotic drugs based on sugars that bind to a target site on the ribosome, the protein factory in the bacterial cell, thus damaging its protein production and causing the bacteria's destruction and death. He also developed sugar-based compounds to repair damaged genes (mutations) that cause genetic diseases such as cystic fibrosis and various types of cancer. These treatment methods are currently being tested in clinical research.
The scientists chemically connected a common antibiotic substance with a catalytic organic molecule that catalyzes and causes the cutting of a chemical bond in the genetic material of the bacterium, and then repeats the same action many times. This leads to the rapid death of the bacteria.
The goal of Prof. Bazov and his team's latest research, which won a grant from the National Science Foundation, was to improve the mechanism of action of the existing antibiotic drugs to solve the problem of bacterial resistance and make it difficult for them to develop new resistance. To this end, they chemically combined (synthesized) an antibiotic of the ciprofloxacin type, which is widely used and has a known resistance problem, and a catalytic organic molecule. This molecule, DNase, catalyzes and causes the cutting of a chemical bond between the building blocks of the bacteria's DNA; and then does not change, and repeats the same action many times. This leads to the rapid death of the bacteria. The mechanism of action of the catalytic antibiotic: a molecule that leads to the target in the bacterium (the yellow triangle), to which is attached the molecule that cuts a chemical bond at the target site (the red bomb)
"The conventional antibiotic drugs bind to the target in the bacteria irreversibly (covalent bond), or in a reversible bond that includes strong interactions between the drug molecule and the target molecule. Both of these types of connections require at least one drug molecule and one target molecule. But in catalytic antibiotics, as we are developing in our lab, one molecule can bind to many target molecules, one after the other, and immobilize them. In this way, in fact, we are turning conventional antibiotics into a new type of antibiotic, catalytic", explains Prof. Bazov.
As part of their research, Prof. Bazov and his team injected the catalytic ciprofloxacin into bacterial cells of various types, performed biological and biochemical tests to examine its antibacterial effectiveness and found that it indeed cuts the bacteria's DNA molecules and thus increases its rate of elimination compared to regular antibiotics. In the future, the researchers intend to further improve the catalytic antibiotic mechanism and test how it might slow down bacterial resistance or prevent it.
We have created a different and more effective mechanism of action of existing antibiotics, but we need to examine its contribution to the resistance problem over the years.
"We have created a different and more effective mechanism of action of existing antibiotics, but we need to examine its contribution to the problem of resistance over the years. The act of cutting the catalytic molecule causes the rapid death of the bacteria, so our hypothesis is that the genetic information that causes resistance is not enough to pass from generation to generation. We hope to improve the existing antibiotics and thus develop new antibiotics, which will better fight the problem of resistance", Prof. Bazov concludes.
Life itself:
Timur Bazov
Prof. Timor Bazov, 68, married + two children and two grandchildren, immigrated from Georgia in 1974 and currently lives in Haifa. His main source of pride is his former students ("leading academics and industry in Israel and the world"). In his free time he likes to cultivate his garden.
