How do Bacteria Develop Antibiotic Resistance

Hundreds of thousands of people around the world die each year from antibiotic-resistant bacteria, and millions of people receiving antibiotic treatment are threatened by resistance. Accordingly, the World Health Organization (WHO) included antibiotic resistance in the list of the top 10 threats to human health in 2019.

Recently, a research team at the University of Cologne in Germany and the University of Uppsala in Sweden developed a model that explained how antibiotic resistance of such bacteria evolves and predicted it, and published it on the 4th of Nature Ecology & Evolution.

A bunch of E. coli magnified 10,000 times with a low-temperature electron microscope. Most of these bacteria, which live in the large intestine of warm-blooded animals, do not harm and maintain symbiotic relationships with the host animal, but sometimes cause serious food poisoning.

The speed and mechanism of development of tolerance is a challenge

Antibiotic resistance has spread greatly, such as the appearance of super bacteria that do not work with existing antibiotics, and medical and pharmaceutical fields have been devoted to clarifying the speed and mechanism by which bacteria develop antibiotic resistance.

One of the goals of these studies is to understand how antibiotic resistance affects bacterial growth and pathogenicity.

Dan I. Andersson, a professor of medical bacteriology at Uppsala University, a senior author of the paper, said, “This kind of knowledge allows us to better track and slow the emergence of antibiotic resistance, thereby prolonging the effective treatment period for antibiotics that prevent bacterial infection. “With this, we can lower the risk of developing resistance by creating new types of antibiotics and possible treatments.”

Bacteria are known to evolve antibiotic resistance through a variety of mechanisms. As a rule, organisms undergo mutations that change their traits as they genetically evolve to adapt to their new environment. Bacteria survive by changing their genome and making them less sensitive to antibiotics.

However, it has been reported that it is difficult to predict which mutations will occur when bacteria adapt to new living conditions. For example, when bacteria move to a new environment with very low nutrient levels, it can be expected to evolve in a direction where limited resources are available. The problem is that it is much more difficult to predict the type of mutation that causes this adaptation.

In this new study of E. coli, the team created a theoretical model that links the degree and type of resistance developed by bacteria with their ability to grow and divide.

A key yet unresolved problem in the study of antibiotic resistance to date has been how the evolution of bacterial resistance affects cell growth at different drug concentrations.

Through experiments, the researchers found that the stronger the bacteria’s resistance to antibiotics, the lower their ability to absorb nutrients. These previously unobserved associations allowed them to predict what kinds of mutations would occur and how much resistance would be conferred when the mutant bacteria were exposed to various concentrations of antibiotics.

As a result of the experiment, certain kinds of mutations occurred when the antibiotic dose was low, and other kinds of mutations occurred when the antibiotic concentration was high. In addition, the resistant mutant cells showed a higher growth rate in the presence of the antibiotic drug, but in the absence of the drug, the growth rate was lower than that of the drug-sensitive wild type.

“Combining Theoretical Model and Experimental Analysis”

Postdoctoral researcher Fermanda Pinheiro, a researcher at the University of Cologne’s Biophysics Institute, the first author of the paper, said, “Mutant cells need to optimize their decisions on antibiotic resistance.” I made it.”

According to Finheyro, bacteria often have multiple options for building a line of defense, making it very difficult to predict mutation evolution. However, in this model, it is possible to successfully predict which resistance mechanisms the bacterial population is likely to evolve under certain conditions.

“The cells in different parts of the bacteria are interdependent and the defense option is determined by the whole system. Changes in mutations in these cell sites leave traces in the growth pattern, so we learn it and ultimately help predict evolution.” You can use it.”

“This work is the first step toward developing a model that links bacterial metabolism and growth with antibiotic resistance mechanisms,” Andersson said. “This will open the way to predict how bacteria will change when exposed to antibiotics.” “It has also been shown that the combination of theoretical models and experimental analyzes is important to understand how bacterial metabolism is optimized under various growth conditions.”

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