A different way of looking at the bacterial population at the School of Medicine of the Hebrew University and Hadassah led to the discovery that bacteria are also equipped with a self-destruction system.
Merit Sloin
One of the most studied topics in biology is programmed cell death. Each cell in the multicellular fortifications has a plan to eliminate the cell. This programmed suicide process occurs when the need arises to get rid of unwanted and harmful cells. Today it is known that the proper functioning of multicellular creatures, including humans, depends not only on the body's ability to constantly produce new cells, but also on its ability to destroy cells.
The process of programmed death is one of the characteristics of multicellular organisms, which is why no one thought to look for such a process in bacteria, which are unicellular organisms. But a different way of looking at the bacterial population at the School of Medicine of the Hebrew University and Hadassah led to the discovery that bacteria are also equipped with a self-destruction system.
More than ten years ago, Prof. Gadi Glazer, from the Department of Cell Biochemistry at the Hebrew University, discovered two genes encoding two small proteins whose role was not clear to him. Glazer called the first "what is it" (mazE); The other is called, respectively, .mazF Prof. Hanna Engelberg-Kulke from the Department of Molecular Biology joined the research about five years ago, and in joint work the two showed that these two genes are responsible for the programmed death of bacteria.
The researchers found that the product of the mazF gene is a long-lived protein that kills the bacteria, while the protein produced by the mazE gene eliminates the toxicity and has a short life. Therefore, in order for the toxic action of the mazF protein to be canceled, the short-lived protein must be produced all the time. "The bacterium lives constantly on the verge of death. At every moment of his life, death is neutralized by creating the short-lived protein," says Engelberg-Kolka. The pair of researchers found that under conditions of distress, when the amount of food is not sufficient for a colony of bacteria, some members of the colony die through the self-destruction mechanism, thus allowing the rest of the colony to exist. In these situations, they found, a special molecule is formed that signals the system to stop the production of the two proteins. The toxic, long-lived protein remains in the cell, while its short-lived friend quickly disappears. As a result the bacterium dies.
"I thought that since the death-anti-death system is always present in the cell, and the actors acting in it are proteins, it is likely that external substances that inhibit the creation of proteins may stimulate it, for example antibiotics," says Engelberg-Kolka. In her laboratory, the hypothesis was tested with a number of antibiotics that inhibit the production of proteins in bacteria, and indeed it turned out that the antibiotics that were tested kill the bacteria through the self-destruction system. "Many antibiotic substances are known to inhibit the creation of proteins in the bacterial cell. Their mechanism of action has been explained so far in that they inhibit the growth of the bacteria and then the body's immune system kills it. From the experiments we performed, a completely different mechanism was discovered," says Engelberg-Kolka.
When the researchers added the antibiotics to bacteria from which the genes responsible for the suicide system had been removed, it became clear to them that the antibiotics indeed inhibited the creation of the proteins, but the bacteria did not die, and only the group that contained the death mechanism died. "The action of antibiotics on bacteria through the death-anti-death system is a new look at the mechanism of action of antibiotics, which raises the possibility of developing a new generation of drugs that aim to stimulate this system," says Engelberg-Kolka. The research work will soon be published in the Journal of the American Society for Microbiology.
Programmed death makes sense in a multicellular creature, but why do bacteria need such a mechanism? Today, the proofs are increasing that bacterial colonies are not just a collection of bacteria found in close proximity to each other, but they are multicellular in nature. "We thought that programmed death in bacteria must be related to their multicellular nature, so we looked for a communication agent involved in self-destruction," says Engelberg-Kolka. In the experiments she conducted with research student Ronan Hazan, it was found that bacteria living densely in a culture liquid secrete into the liquid a protein that triggers the death mechanism. The researchers believe that this protein is the communication substance they were looking for and they called it "extracellular death factor".
"According to our concept, a bacterial colony can be viewed as having a multicellular nature," says Engelberg-Kolka. "Three characteristics are accepted today in multicellular organisms: programmed death, communication between cells and differentiation into cells with defined functions. Two of them we have already shown to exist in bacterial culture. As for the third factor, the ability to differentiate, in my humble opinion not all bacteria are the same. It is a fact that in situations of nutritional stress, some bacteria die and others remain alive. But are there really any differences between them? This must be proven."
{Appeared in Haaretz newspaper, 3/8/2000{
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