Alexandra Bruther: genetically engineering antibiotics

Alexandra Bruther Sparktography/Flickr

Since Alexander Fleming opened Penicillin, a new era began in medicine. Diseases and wounds, which often turned out to be fatal before, now no longer look so threatening. The risk of developing dangerous infections after surgical interventions was reduced to a minimum. But antibiotics have two problems: non -specific and antibiotic resistance . Both of these problems in one fell swoop will solve the approach proposed by the American-French group of scientists in the journal Nature Biotechnology .

Antibiotics have a certain mechanism of action. Some perfume the cell wall of the bacteria, others inhibit the work of a certain bacterial enzyme, and others do not allow bacteria to synthesize protein. Antibiotics are relatively harmless to humans (in comparison, for example, with drugs for the chemotherapy of cancer), because the molecular mechanisms of bacteria and a person are very different. The substance inhibiting the work of ribosomes of the bacteria will not inhibit a person with a ribosoma.

But in the human body there lives a lot of harm or even beneficial bacteria. Antibiotics act on them in the same way as pathogenic bacteria. Their death is undesirable for a person. The death of symbiotic bacteria in the gastrointestinal tract can lead to problems with digestion of food. In addition, in the human body, on the skin and mucous membranes of the population of different types of bacteria and fungi are in fragile balance. Representatives of different species restrain each other, the immune system monitors them all, and no one bothers each other. The reduction in the number of bacteria of one sensitive to the antibiotic, the species often entails the expansion of bacteria of a different type or mushrooms that did not bother in peacetime, and the body has to deal with another infection. Of course, this is not so scary to refuse to take antibiotics when there are evidence for this, but quite unpleasant.

The problem associated with resistance to antibiotics is much more serious. DNA of bacteria, like DNA of any other organism, mutates. In stressful conditions, even faster than usual. For example, if the antibiotic used should inhibit a bacterial enzyme, then in the gene encoding this enzyme, a mutation can occur in such a way that the resulting new enzyme will also cope with its function, and there will no longer be inhibited by the antibiotic. Having received this mutation, the bacterium will successfully multiply in the presence of an antibiotic, and the patient will not recover.

In the most advanced cases, the bacterium is made stable to several antibiotics at once. In such cases, they talk about polyuretrality. Polyurezistivity of the bacteria of tuberculosis today has become a very noticeable problem. Cases have become more frequent when, with all the successes of modern medicine, the patient does not manage to help. The problem of antibiotic resistance enhances the ability of bacteria to exchange genes among themselves. The Gene, which gives bacteria stability, may not be encoded in the bacteria genome, but in plasmide - a small DNA molecule that exists separately from the main genome. Plasmides can get from one bacteria to another or from a bacteria to the environment (for example, after its death), and from there to a new bacterium, removal of papillomas . Many bacteria, having felt that their affairs are bad, can even strengthen their susceptibility to plasmids from the surrounding world.

The method developed by the authors of the article allows you to kill only pathogenic bacteria or destroy plasmids inside bacteria that give resistance to antibiotics.

Scientists adopted the CRISPR/CAS9 system (we already wrote a little about it ), borrowed from bacteria. In bacteria, CRISPR/CAS9 plays the role of the immune system. Due to the presence in the genome of sequences that coincide with the DNA of enemies of bacteria - bacteriophages , bacteria recognize bacteriophages at the early stage of the infection, and CAS9 protein cuts the DNA of phages. The mechanism of this is similar to the RNA interference mechanism. After previous infections, fragments of its DNA remain similar to the bacteriophage in the genome. RNA is synthesized from them. According to the principle of complementarity, this RNA interacts with the genome of the new phage, with the help of other proteins, the CAS9 protein recognizes this structure and cuts it. If you artificially synthesize the desired RNA, complementary to any pre -selected sequence, and enter it into the cells along with the structure encoding the CAS9 protein, then any DNA in the cell will be cut in the selected place.

The authors of the work synthesized genetic constructions encoding CAS9 protein and sequences, complementary genes that are responsible for pathogenicity and resistance to antibiotics in staphylococcus aureus golden staphylococcus. They packed these designs in bacteriophages and infected with these bacteriophages harmless S. aureus , pathogenic strains and strains resistant to antibiotics. It turned out that the bacteria of a non -laundry strain were not injured, pathogenic died, and the stable lost stability. Nepatogenic and unstable strains after such processing could no longer become pathogenic or stable, capturing plasmid from the environment, because the structure remained in the cells forever.

Of course, this method is much more expensive than chemically synthesized antibiotics, but some infections no longer leave a choice.

See also: Maxim Rousseau goat instead of the pharmaceutical factory Alexander Bruther History of pharmacology Medicine at the genomic level Survival race