According to WHO, antibiotic resistance is a global problem today, with ever-increasing proportions every year. According to experts, we may soon encounter problems of the “pre-antibiotic” era if we do not take serious steps in this direction.
We all know perfectly well that antibiotics are medicines designed to fight bacterial infections. In some cases, they are used not only for treatment but also for prevention. For example, for the prevention of infections in the preoperative period.
Resistance in humans or bacteria?
One of the biggest misconceptions is that resistance to antibiotics occurs in the human body. In fact, bacteria stop responding to antibiotics, not people. As the process develops, the effectiveness of drugs gradually decreases and eventually is completely lost. The further spread of resistant strains causes intractable infections.
Drug resistance is a natural course of evolution. But misuse of antibiotics can speed up this process.
Under the influence of antibacterial drugs, the most sensitive microorganisms die, and those resistant to treatment survive. Subsequently, they can multiply, transmit resistance to their offspring, and in some cases to other bacteria.
Resistance mechanisms are the subject of scrutiny in the world. But they are not so interesting as the reasons for this process.
Reasons for the development of resistance
WHO identifies several causes of drug resistance:
- Irrational use of antibiotics (the use of antibiotics without evidence, the use for a too short period, the use in too small doses);
- Use in veterinary medicine and livestock for growing crops.
In countries where antibiotics can be purchased freely at the pharmacy, the likelihood of the emergence and spread of resistant strains is much higher. This fully applies to excessive use of antibiotics of without indications.
Antibiotic resistance can affect every person at any age and in any country.
Complete misunderstanding
WHO, as part of a global initiative, conducted a full-scale survey in which about 10 thousand people from 12 countries took part. The survey results showed a lack of understanding of the problem, the mechanisms of occurrence and the severity of the problem.
For example, the vast majority of respondents (76%) believe that antibiotic resistance occurs in the human body. About 64% – that colds and flu can be treated with antibiotics, although antibacterial drugs do not affect viruses. Almost a third (32%) of respondents believed that it is necessary to stop taking antibiotics with an improvement in well-being instead of completing the prescribed course of treatment. Almost half (44%) of respondents believe that antibiotic resistance is a problem only for those who regularly take them. In fact, any person of any age in any country can get an antibiotic-resistant infection. About 64% believe that doctors will solve this problem before it becomes too serious.
History of the problem
The discovery of penicillin in 1928 can be compared with the revolution in medicine. The euphoria did not last long – pretty soon penicillin-resistant staphylococci began to reveal. The first penicillin-resistant strains of Streptococcus pneumoniae were discovered in Australia in 1967, and some time later, penicillin-resistant bacteria were detected in the United States in a patient with pneumococcal meningitis.
The second antibiotic – tetracycline – was synthesized in 1950, while in 1959 the first Shigella resistant to it was revealed. Widely used in the 1950s, kanamycin has completely lost its therapeutic effect nowadays due to the predominance of kanamycin-resistant strains.
Another striking example is the emergence of multidrug-resistant Staphylococcus aureus. This is a dangerous strain of methicillin-resistant Staphylococcus aureus, which causes sepsis and pneumonia, which are difficult to treat. Most often, nosocomial infections are associated with this pathogen. However, a household methicillin-resistant staphylococcus appeared in 90s. In recent years, it has become increasingly common to talk about multidrug-resistant tuberculosis, which does not respond to the two most powerful anti-TB drugs – isoniazid and rifampicin.
How to deal with antibiotic resistance?
Slow down the spread of resistance
The US and Europe have realized the magnitude of the problem and are acting. Measures are being taken to slow the spread of antibiotic resistance: it is forbidden to add drugs to the feed that are used to treat a person; and many European countries do not allow the use of antibiotics to stimulate the growth of animals and birds.
They fight against the unreasonable prescription of antibiotics for viral or fungal infections, the initiative of patients in antibiotic therapy, and the sale of antibiotics without prescriptions. Instead of using drugs with a wide spectrum of action, drugs of a narrow spectrum are used, if possible: with a focused impact on a specific type of bacteria, resistance develops more slowly.
And, of course, each person can contribute to the fight against resistance by taking antibacterial drugs exactly as prescribed by the doctor, by completing the course of the antibiotic. Alas, some countries are not fully included in this struggle.
Develop vaccines
One more solution to the problem of antibiotic resistance is to prevent the development of infection. For this, vaccination is widely used. Unlike antibiotics, bacteria do not develop resistance to it: the vaccine does not fight against specific strains but creates a specific immunity against them in advance.
Of course, the development of new vaccines is necessary, including for the prevention of infections such as staphylococcus aureus and other aggressive and “resistance-catching” microbes. Of course, no one is stopping the microorganisms from evolving, like the flu virus doesL scientists can create a new vaccine against it every year. Nevertheless, the composition of the vaccine is almost always able to be made quite effective. However, staph vaccines show only limited and short-term effectiveness, so development continues.
“Spoil” the bacterium at the cellular level
Many antibiotics work that way. Antibiotics can interfere with the synthesis of the cell membrane of the microorganism, the cell wall, the synthesis of nucleic acids, amino acids, proteins. However, the former drug targets were enzymes or peptides associated with protein assembly steps. In turn, bacteria can mutate and change the structure of their enzymes, making them inaccessible to drugs or make the antibiotic inactive, or reduce the permeability of the antibiotic, and even “push” the antibiotic from itself.
Recently, there has been active development of new antibiotics that interact with such basic structures inside the bacterium that they cannot immediately change them and adapt.
So, in 2016, a substance was found in the human nose that acts against especially dangerous bacteria of the species Staphylococcus aureus (MRSA) (this bacterium also belongs to staphylococci, but does not harm the body). This substance is called “Lugdunin” in honor of the bacterium that synthesizes it. Lugdunin has an unusual chemical structure and may be the prototype for a new class of antibiotics – Fibupeptide.
Another substance synthesized by the bacterium Eleftheria terrae is called Teixobactin. It overcomes many types of drug resistance (including multidrug-resistant tuberculosis). This substance targets molecular complexes that the bacterium cannot change by mutations, therefore there are no ready-made genes against teixobactin in nature, and it cannot “pick up resistance” from another bacterium. True, it is possible that over the years, bacteria will still find a way and even adapt to teixobactin. But gaining time is also important.
There may be other approaches to exposure to bacteria – for example, a combination of an antibiotic with molecules of the class of alkylresorcinol. These are molecules that release plants and bacteria into the environment to protect against external factors and parasites. Alkylresorcinol spoils the bacterium from the inside, acting immediately on the cell membranes, and on the proteins, and on the genome, which makes it possible for the antibiotic to act on it. Biologists called the combination of an antibiotic with alkylresorcinol “super-bullet”: the effectiveness of treatment increases by 1000 times and the development of resistance slows down by 10-30 times.
Menachem Shoam of the University of Cleveland infected mice with antibiotic-resistant staphylococcus (deadly MRSA bacterium, which cannot be cured now), waited for sepsis, and injected them with molecules that prevent the bacteria from producing toxins. All mice survived, while two-thirds of infected animals died without treatment.
Another way to enhance the effect of the antibiotic was proposed by scientists from Boston University. They added silver ions to the antibiotic. Knowing the antiseptic properties of silver, the researchers suggested that a modern antibiotic with the addition of a small amount of this substance can kill 1,000 times more bacteria.
Take the enemies of our enemies as allies
Another promising and yet not very well-studied area of struggle is the development of bacteriophages, viruses that infect bacteria. These viruses are as volatile as the bacteria themselves and can adapt to their resistance. But this requires all the time to collect and update the “collection” of bacteriophages.
So, in 2018, Graham Hatful from the University of Pittsburgh saved a fifteen-year-old girl with cystic fibrosis. After a lung transplant, her body was attacked by antibiotic-resistant bacteria, and she would have died if the experimental treatment had not been used: the doctors introduced her with genetically modified viruses that kill this type of bacteria. The girl recovered, and the bacteria showed no signs of resistance to viruses.
Wean bacteria to develop resistance
This, of course, is the most reliable way. Therefore, the resistance mechanism is now thoroughly studied so that it is possible to edit the bacterial genome and wean it to mutate. Using the CRISPR genome editing method, several key biochemical processes in cells are disrupted. The method is called CHAOS (Controlled Hindrance of Adaptation of OrganismS – “controlled suppression of adaptations of organisms”). After that, the good old antibiotics will work again, and we will be able to live with bacteria in a state of controlled war. But this method is still being developed.
Who evolves faster – bacteria or us? We will learn the answer to this burning question in a few decades.