The five major hazards of bacterial resistance, the causes of bacterial resistance

Where a few tens of units of penicillin used to save lives, today millions of units may not produce any effect. During the heyday of antibiotics in the 60s, when about 7 million people worldwide died each year from infectious diseases, this figure has risen to 20 million this century [6]. Even if an individual has not abused antibiotics, they may be infected with resistant bacteria that have been cultured as a result of overuse of antibiotics.

Approximately 450,000 new cases of MDR-TB emerged in 2012, and XDR-TB is now present in 92 countries and territories, and these patients with drug-resistant strains have to face longer treatment courses and poorer outcomes [7]. The spread of extensively drug-resistant tuberculosis, artemisinin-resistant malaria and third-generation cephalosporin-resistant gonorrhea like a plague around the world means that these diseases we have conquered may once again become incurable diseases for all mankind. The pathogens we will face in the future will be enhanced versions of those of a hundred years ago, and there is an urgent need to develop new drugs based on new targets to deal with them.

After all, the development of new drugs is a huge project, and it is difficult to catch up with the speed of bacterial mutation. If drug-resistant bacteria cannot be controlled, it will no longer be a matter of personal cost, but an economic burden on the whole society.

Bacterial resistance to antimicrobial drugs, also known as drug resistance, generally refers to a state in which bacteria respond to drugs as a whole, which can lead to reduced drug efficacy or failure.

The main causes of drug resistance are:

1) Factors of bacteria themselves: Bacteria can develop drug resistance through mutation or acquisition of drug-resistant plasmids, and a bacterium can become resistant to antimicrobial drugs through a variety of drug resistance mechanisms. (2) Antimicrobial drugs are widely used in nature, and only a small number of natural drug-resistant bacteria exist in nature, and it is difficult to compete with the dominant susceptible bacteria, and only after the susceptible bacteria are killed in large quantities due to the selection of antimicrobial drugs, drug-resistant bacteria can multiply in large numbers and become dominant bacteria to replace the position of sensitive bacteria and cause infection. (3) The drug resistance mode and drug resistance rate of bacteria blindly applied broad-spectrum antimicrobial drugs were different among ducks and regions, and there was a lack of understanding of the flow of bacterial resistance in the region, and the blind application of broad-spectrum antimicrobial drugs led to the emergence of drug resistance.

4) The lack of combination drugs and the lack of combination of antimicrobial drugs are one of the important reasons for drug resistance.

Some drugs may slowly become ineffective because bacteria develop resistance.

Antimicrobial resistance is a phenomenon in which bacteria are not sensitive to antibiotics, and the cause is a special manifestation of bacteria in the process of their own survival. Natural antibiotics are secondary metabolites produced by bacteria that are used to defend themselves against other microorganisms.

Humans make antimicrobial drugs into antimicrobial drugs produced by bacteria to kill infected microorganisms, and microorganisms that come into contact with antimicrobial drugs will also resist antimicrobial drugs by changing metabolic pathways or producing corresponding inactivated substances.

It is easy for people to ignore that pathogenic microorganisms are also a kind of organisms, and when people pick up antibacterial drugs to "kill" them, pathogenic bacteria have also evolved various means in order to reproduce their own race, such as generating enzymes that hydrolyze antibiotics to make them ineffective, or making antibiotics unable to enter pathogenic bacterial cells, etc., and passing on these resistance genes to the next generation. It has to be said that this is an inevitable process of evolution in nature, and we cannot change it.

Essentially, genetic mutations are the root cause of bacterial resistance, but without the misuse of antimicrobials, the problem would not be so intractable. Why? Because, genetic mutations are a common thing in nature.

Accidental genetic mutations can form a small number of resistant strains that are not susceptible to antibiotics, but it is almost impossible to achieve perfect resistance to a pathogen with a single mutation. In reality, drug resistance is a gradual accumulation, from quantitative to qualitative change. If people can use antimicrobial drugs in a standardized manner, most of the pathogenic bacteria will be killed or inhibited, and some "survivors" will also be wiped out by the body's immune system.

However, due to people's lack of understanding of antimicrobial drugs and long-term non-standard use, some pathogenic bacteria that are sensitive to bacteria are killed, and the drug-resistant bacteria that are not dominant remain and multiply from generation to generation, and the drug resistance genes have become stable and solid. What's even worse is that some drug-resistant pathogens can share these genes in other pathogenic populations. Over time, there will be more and more pathogenic bacteria carrying drug resistance genes, which will also bring great difficulties to **.

Once resistant bacteria are found, they are killed by other methods so that they do not multiply to the next generation. It is also possible to culture bacteria without drugs.

The generation of bacterial drug resistance can be caused by the mutation of bacterial chromosomal drug resistance genes, the transfer of drug resistance plasmids and the insertion of transposons, so that bacteria can produce some new enzymes or polypeptides, destroy antibacterial drugs or block the penetration of drugs into target cells, or occur new metabolic pathways, thereby producing antibiotic resistance and causing the failure of clinical drugs.

It's not that bacteria become resistant because of the use of antibiotics. In the process of bacterial reproduction, the genetic material of some bacteria is changed, that is, genetic mutations, resulting in bacteria having drug resistance, antibiotics only play a screening role, after the use of antibiotics, resistant bacteria will survive, and bacteria without drug resistance will die.

In fact, most antibiotics have similar components, and their resistance mechanisms are similar, either changing the action of enzymes, or destroying the internal structure of bacteria, etc., in this case, it may lead to a bacterium being resistant to a variety of antimicrobials. And, natural selection by the environment may also lead to those outcomes you are talking about. The role of drug resistance is not absolute.

Bacteria develop resistance to antimicrobial drugs through genetic mutation, etc. In layman's terms, an antimicrobial drug is effective at the beginning of use, but after a period of time, it is found that the efficacy decreases, which may be due to bacterial resistance to the drug. Generally, it can be confirmed through etiological examination and antimicrobial susceptibility testing, and the specific mechanism of drug resistance is not to be mentioned, anyway, there are too many.

Because there are some bacteria whose genes themselves determine that they are not afraid of this drug, those who are afraid of this medicine are dead, and the rest are not afraid, so these bacteria that are not afraid continue to multiply, and there are more and more offspring, and there are many bacterial genes that are not afraid of this drug, and in the end, most of the bacteria are not afraid, which means that the bacteria have developed drug resistance, which is also a natural selection process for bacteria.

The evolution of drug-resistant strains is a natural phenomenon of survival of the fittest. With the advent of antibiotics, strains that are sensitive to drugs have been killed one after another. However, as the microorganisms themselves reproduce from generation to generation, accidental genetic mismatches can form a small number of mutant strains that are not sensitive to drugs.

Genetic mismatches are something that happens all the time in nature. For example, in this very second, a mutant bacterium may emerge from the E. coli in your gut. But for a "fortuitous mistake" to be meaningful and impactful, it takes a lot of fecundity.

And that's where bacteria come in.