Custom-made instinct
Scientists have figured out how to trick the receptors of pathogenic bacteria
Maria Nedyuk, Izvestia
Scientists from MIPT investigated two sensory abilities of microorganisms: "sense of smell" and "sense of elbow". The first helps microbes interact with surrounding cells and understand what is happening around them. The second gives them the opportunity to communicate with each other and, for example, attack the human body with a malicious colony. Russian researchers have studied the receptors that help bacteria to "make friends" and "sniff" at the structural level, and realized that the development of any infection can be stopped by destroying these sensory abilities. In the future, the technique of "deception" of the senses of the "quorum" and the smell of bacteria will allow scientists to defeat many diseases.
Bacterial "nose"
It turned out that bacterial communication is possible due to specific proteins, Ivan Gushchin, head of the Laboratory of Structural Analysis and Engineering of Membrane Systems at MIPT, told Izvestia.
– We are engaged in membrane proteins. Every cell – both bacterial and human – is covered with a membrane membrane," he explained. – While some proteins float inside the cell, many sit in the membrane and are responsible for the communication of this cell with the outside world.
Bacteria communicate through the exchange of substances with the environment. The process of how bacteria learn what is happening around them is called "olfaction". Scientists have studied the membrane receptors of bacteria, which allow them to "smell" (feel) what substances are around. On average, one bacterium can have about 25 such receptors. Ivan Gushchin and his colleagues were the first in the world to obtain an X-ray image of the crystal structure of the membrane part of such a receptor. For this work, the equipment of the research center in the city of Julich (Germany) was used.
– The receptor itself is a protein molecule that penetrates the membrane. And it has two parts. The part that is located outside the membrane, binding to the signaling molecule of the substance from the outside, changes its structure. This change is transmitted through the transmembrane region into the cell. This inner part begins to phosphorylate, that is, to form phosphoric acid esters. The reaction occurs only when the outer part of the protein has bound its signaling molecule," Ivan Gushchin said.
By this reaction that takes place inside the cell of the bacterium, it learns what is happening outside. For example, if a certain nutrient has been received from the outside, then the bacterium begins to secrete enzymes to digest it. If this is a danger signal, then the bacterium begins to produce special "offensive" proteins – toxins.
Further studies of the "sense of smell" of bacteria will allow scientists to better learn how the instigators of infections are arranged and learn how to deceive them. For example, if a bacterium "smells" a wound on a person's body, it can move towards it. And if you "deceive" the receptors of the "sense of smell", the microbe can simply go on the wrong track.
Such deception of microorganisms will contribute to the fact that in the future a person will not need to kill bacteria to save himself from diseases, which is especially important in conditions when microbes develop resistance to antibiotics. It will be possible to simply disrupt the "sense of smell" of a pathogenic bacterium.
Microbes are on the attack
However, it is not only the sense of smell that allows bacteria to attack the human body. Another sensory ability of bacteria that is being studied at MIPT is the "sense of quorum", or "sense of elbow". It is it that gives microorganisms the opportunity to communicate and coordinate their behavior through the secretion of molecular signals.
– We are studying the sensors that are responsible for this ability to interact, – said Ivan Gushchin. – It is directly related to the occurrence of infection. The bacterium is afraid to attack the body alone – the immunity will overcome it. Therefore, microbes choose such a strategy: they first multiply imperceptibly, and at the moment when they realize that there are a lot of them, they begin to attack.
In order to find out how many of them, bacteria constantly throw out certain substances. It is their concentration that makes it clear whether there are enough "microscopic soldiers" to attack. If this cellular mechanism is destroyed, it is possible to prevent the formation of pathogenic colonies – biofilms. At this stage, MIPT scientists are studying the structure of one of the receptors responsible for the "elbow feeling".
– The signaling molecule acting on this receptor, which is called QseC, is not known – and this is one of the reasons why we are working with it, – said Alina Rameeva, Deputy head of the Laboratory of Structural Analysis and Engineering of Membrane Systems at MIPT. – Having a large amount of protein in our hands, we can try to check the binding of various substances, and if we can determine the structure of the protein, then perhaps we can guess the signaling molecule by the shape of the pocket in the protein that binds it.
Complete victory over infections
In the future, the knowledge gained will help scientists to "dissect" bacteria. Researchers will have the opportunity to figure out how to destroy the signaling molecule, for example, by introducing an antibody that will bind it, or an enzyme that will cleave it. This, in turn, will allow us to find a mechanism for destroying infections without the use of antibiotics.
The facts that bacteria receive a lot of information about the environment and are able to communicate, thereby coordinating their actions, have been known for a long time. However, many of the molecular mechanisms underlying this process have not been sufficiently studied so far, Director of the Institute of Molecular Medicine at Sechenov University Andrey Zamyatnin told Izvestia.
– The work of scientists from MIPT makes it possible to better understand such mechanisms, which means that it provides new opportunities for controlling the behavior of microorganisms, – the scientist noted. – Knowledge can be useful both in medicine in the treatment of infectious diseases, and in biotechnology, including in the production of food products, where a wide variety of microorganisms have been used for a long time.
The results of the research of Physicist scientists may become the basis of medicine of the future, suggested Alexander Kagansky, head of the Center for Genomic and Regenerative Medicine of the School of Biomedicine of the FEFU (university – participant of the project "5-100").
– There is a feeling that researchers have looked at the next page of the development of medicine. I think there is still a big practical part ahead. Learning how to synthesize deceptive molecules or mislead bacteria in another way is a huge job," he said.
The research of the senses of "smell" and "elbow" at Phystech is supported by the Russian Scientific Foundation.
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