The World Health Organization announced the problem of antibiotic resistance in 2014, which is being progressed in different countries in different countries. The phenomenon of antibiotic resistance is a threat to people's lives - a person can die from a banal infection or a small injury like 300 years ago. WHO predicts about 10 million deaths per year by 2050.
Scientists from the Federal Scientific and Clinical Center for Physico-Chemical Medicine, the Moscow Institute of Physics and Technology and the Data Laboratory created ResistoMap - an interactive map of the intestinal resistome - the presence of drug resistance genes in the human intestinal microbiota. The microflora of this organ is dominant in number over other organs. It weighs about two kilograms and has ten trillion microorganisms. In the intestinal ecosystem it is encoded a hundred times more genetic information than in the human genome. The state of the biological defense system, hemostasis and homeostasis, the normal digestion of a person is largely determined by the stability of his microflora. For example, Crohn's disease is a disease of the colon that mimics almost any other disease, and all because of a violation of nutrients absorption.
ResistoMap consists of a geographical and heat map. In any location, we can get a cut of the resistome - a set of resistance genes. Data is filtered by country, gender, age and diagnosis. The pattern of the map is such that in countries with limited use of antibiotics in treatment the resistance is lower. In Russia, China and France antibiotics are available without a prescription and often prescribed for common colds, and such uncontrolled use harms the immunity of society.
The rules that follows from the card have been known for a long time: one must use antibiotics strictly as prescribed by a doctor, carry out treatment to the end, do not change the dosage, do not overload it, identify pathogens, if possible, and treat with narrow spectrum antibiotics.
How drug resistance develops: antibiotics inhibit a microbe-specific metabolic process by binding to an enzyme or structural molecule. Antibiotic resistance genes are present in the natural microflora initially, but increase during treatment with antibiotics and can be transmitted to the pathogenic microbe. True natural resistance is characterized by the absence of the target's microorganisms' action of the antibiotic or the inaccessibility of the target for the biological protection system due to the initially low permeability. This phenomenon is a constant species trait of microorganisms and is easily predicted.
The mechanisms of antibiotic resistance include modification of the target, inactivation of the antibiotic, active elimination of the antibiotic from the microbe, impaired permeability of the shell of the microbe, the formation of the metabolic "shunt".
The work of evolution in the form of a complex system of biological protection of individual microorganisms can be seen in the example of their individual groups. β-lactam antibiotics, for example, are inactivated by all microorganisms (and this is all of them except staphylococci) by hydrolysis.
Plasmid extended-spectrum beta-lactamase (BLRS) of gram-negative bacteria are most important for clinical practice, since they are capable of destroying III and IV generations of cephalosporins and are difficult to diagnose. In Russia, the prevalence rate of these enzymes among hospital Klebsiella reaches 90%.
The decrease in the permeability of the outer membranes of gram-negative bacteria is an obstacle to the penetration of β-lactams into the cell, this is achieved by mutation of the “porin channels” of the microbe. P.aeruginosa has biological defense systems that actively remove carbapenems from the cell. The PSB enzyme of staphylococci and pneumococci, which synthesizes the cell wall, mutates. As a result, the affinity for β-lactams is reduced.
Aminoglycosides are inactivated by enzymatic modification, losing the ability to bind to the ribosomes of the bacterium — they are bound to acetic or phosphoric acid molecules, or to adenine. The frequency of resistance among gram-negative bacteria to gentamicin and tobramycin is high in Russia, due to their unjustifiably widespread use. Gram-positive bacteria synthesize the bifunctional enzyme AAS (6 ') - APH (2' '), destroying the majority of aminoglycosides, except streptomycin and spectinomycin. Natural resistance to aminoglycosides in anaerobes is explained by the fact that these antibiotics pass through the cytoplasmic membrane via electron transfer channels, which are absent in anaerobes.
Resistance to quinolones is manifested by the modification of the target of action - two bacterial enzymes of DNA gyrase and topoisomerase IV - that will disrupt the replication of the pathogen. In Russia, resistance to fluoroquinolones (ciprofloxacin and ofloxacin) is most often formed within the strains of P.aeruginosa
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