Both the survival and violence mechanisms developed by amoebas during evolution are a mystery and research subjects that fascinate scientists (although relatively few) from different parts of the world, including the Weizmann Institute of Science
From right to left: Rivka Bracha, Prof. David Mirelman, Yael Nochamowitz and Prof. Carlos Gitler. The amoebas are coming
Millions of people are infected every year, and thousands of them die, from intestinal diseases caused by amoebae, which are parasitic single-celled microorganisms. Diseases caused by amoebas mainly attack populations living in poor and backward countries where the level of sanitation is poor, because the drinking water is contaminated with sewage. So far, almost no new ways have been developed to fight these diseases, and this is, among other things, because the number of research groups studying these diseases is relatively small. The fact that the population affected by this type of disease is usually backward and poor is not a sufficient financial incentive for large pharmaceutical companies to enter the thick of the beam. However, both the survival and violence mechanisms developed by amoebas during evolution are a mystery and research subjects that fascinate scientists (although relatively few) from different parts of the world, including the Weizmann Institute of Science.
The story of such research conducted at the institute begins in the early 80s, when Prof. Carlos Gitler and Prof. David Mirelman
The Department of Membrane Research and Biophysics (now the Department of Biological Chemistry) received a joint research grant from the Rockefeller Foundation to study the amoebae that cause dysentery. Prof. Mirelman then focused on researching the proteins (lectins) that allow the amoeba to attach to human cells, while Prof. Gitler discovered that amoebas have a special small protein that, after they attach to human cells, they "inject" it into their membranes, which causes their death. This phenomenon was called "the amoeba's kiss of death". This violent killing of cells, and the invasion into the intestinal lining, causes the disease of dysentery, which was called by the Spanish, who conquered Mexico in the 16th century, "Montezuma's revenge".
Prof. Gitler, who immigrated to Israel from Mexico, saw with his own eyes the great suffering caused to many people in Mexico suffering from intestinal diseases caused by amoebas. He called the special protein he discovered "Ambaphor", and hoped that by means of antibodies developed against this protein it would be possible to curb the damage of the amoebas. But then it turned out that the antibodies cannot reach the amphore and stop it, because the amoebae attach their membrane to the membranes of the target cells, so that the amphore passes from them directly to the target cell, when it is hidden between the two membranes, and the antibodies cannot reach it.
About 15 years later, Prof. Mirelman, and the members of his research group, Rivka Bracha and Yael Nochamowitz, also began to investigate the Ambpur with the aim of proving its role in the development of the disease. To this end, they used a special technique of genetic engineering against the deadly protein, based on inhibiting the transcription process of genes. As we know, the process of producing a protein begins when the gene that encodes the information needed for its construction is opened, and a single-stranded messenger RNA molecule is formed in front of its information-carrying strand. The messenger RNA exits the nucleus into the cell cavity, where it reaches the ribosome, which translates the information contained in it and produces a protein based on it (in this case, it is the ambaphor protein, which allows amoebas to kill target cells). Prof. Mirelman and the members of his research group isolated the gene coding for ambaphor, and returned and inserted a copy of it (using a plasmid prepared
especially for this purpose) to the amoeba's genetic load, with its nucleotide order reversed ("anti-sense"), that is, with its "tail" pointing "forward" and it is a perfect mirror image of the original gene that encodes the information for building the amoeba. Thus, in effect, a transgenic amoeba was created that carries both the original amphophoric gene and the reverse gene. When the lambda gene starts to express, so does the reverse gene (which is on the plasmid). Thus, simultaneously with the creation of messenger RNA, which should cause the production of the lethal protein, a reverse messenger RNA molecule is also produced. These two molecules, which fit in exact reverse to each other, stick together like the two parts of a zipper. As a result, both are not available for "translation" and the creation of the amphophor protein. In this way, the scientists were able to inhibit by about 60% the production of the lethal protein in the transgenic amoebas.
The amoeba that were "engineered" in this way were much less violent than the original amoeba, but the scientists were not satisfied with this result. Indeed, in a follow-up study they succeeded in causing the complete silencing of the gene encoding the lethal protein (that is, to prevent its expression). The phenomenon of the complete silencing of the gene took place when the scientists injected into the amoeba a plasmid that carried a copy of only the initiating segment (promoter) of the lambphor gene. Prof. Mirelman says that the presence of additional copies of the initiating segment of the gene caused an enzymatic reaction that added putative groups to this genetic region. It is known that such a reaction causes the silencing of genes in plants and other cells, but this is the first time that such a phenomenon has been observed in amoebas.
After the amoebae completely stopped producing the ambaphor, the scientists extracted from them the plasmids carrying the initiator segment of the ambaphor gene. But, the Lambpur garden silencing phenomenon continued.
This phenomenon is known in other types of cells as epigenetic inheritance. In this way, the scientists were able to develop a new species of amoebas that do not produce amphophora, and are therefore unable to harm humans. Now the researchers plan to try to use the "silenced" amoeba as a means of vaccination against violent amoeba.
As you know, to vaccinate the body against any viral disease it is possible to use killed or weakened viruses. When such viruses are introduced into the body, they cannot cause disease, but the components of the immune system learn their characteristics, and thus, when violent viruses enter the body, the immune system is already prepared for them and is able to stop their spread in the body. In similar ways, scientists are also developing vaccine components against diseases caused by bacteria, but so far this technique has not been used to vaccinate against diseases caused by amoebas. The weakened amoebae developed by Prof. Mirelman, which are unable to produce the deadly protein Ambaphor, may form the basis of the first vaccine of this kind. If the scientists succeed in this task, it will open the door to great relief among millions of people suffering from diseases caused by amoebas.
oxidation-reduction
Tea and rice are available in China, but the poor sanitary conditions that prevail in the rural areas of this vast country help the spread of amoebas that cause serious intestinal diseases. Hundreds of millions of Chinese who manage to defend themselves against amoebas owe thanks to one of their ancestors, who about five thousand years ago discovered the medicinal properties of a special alcoholic garlic extract. Prof. David Mirelman, who visited China about ten years ago, was surprised to discover that this alcoholic garlic extract kills the amoebae that cause the disease, while it is not harmful to the humans who drink it.
When he returned to the Weizmann Institute of Science, he began to investigate the meaning of the mystery. He discovered that a molecule found in garlic, called allicin, oxidizes and destroys certain enzymes essential to the amoeba, thus causing its death. In fact, the same substance damages the enzymes in human cells in the same way, except that human cells have a kind of defense mechanism based on molecules of a substance called glutathione. The glutathione molecules restore the enzymes that were damaged by allicin, thus repairing and returning them to normal operation in human cells. To the misfortune of the amoebae, and to the good fortune of humans,
The amoebae, like other microorganisms, lack glutathione, so they remain exposed and defenseless against
Allicin in garlic. These days, attempts are being made to develop, based on allicin, ways to treat intestinal diseases caused by amoebas.
Prof. Mirelman on the Great Wall of China. Which is good for a billion people
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It's nice to read about scientific confirmation for one of the more common grandmother's remedies - garlic.
Active vaccination of weakened amoebae is a good idea.
On the other hand, the question arises as to why our adaptive immune system is not able to fight effectively against the pathogenic amoebae. Their identification as a foreign agent does not have to be based on the amoeba, but on many foreign molecules that characterize the amoeba, which are more exposed and accessible to the immune system compared to the amoeba. What "camouflage and evasion" mechanisms does the amoeba use to defend itself against the intensive monitoring of our immune cells?
A no less good solution is the development of a molecule that will bind specifically to ambophor and inhibit its activity. For this, of course, the three-dimensional structure of the protein needs to be deciphered.