Study sheds light on antibiotic resistance, fitness landscape

New Mexico (ANI): E. coli bacteria may be more capable of acquiring antibiotic resistance than scientists previously thought, according to a recent study published in Science.
Led by SFI external professor Andreas Wagner, the researchers experimentally mapped more than 260,000 possible mutations of the E. coli protein, which is essential for the bacteria’s survival when exposed to the antibiotic trimethoprim.
During thousands of highly realistic digital simulations, the researchers found that 75% of all possible evolutionary paths for E. coli proteins ultimately endowed the bacteria with such a high level of antibiotic resistance that a physician would no longer prescribe antibiotics. Trimethoprim to a patient.

“In summary, this study suggests that bacteria like E. coli may be more efficient at developing resistance to antibiotics than we initially thought, and it has broader implications for understanding how evolutionary biology, chemistry How different systems adapt and evolve is important in science and other fields, says Wagner, an evolutionary biologist at the University of Zurich in Switzerland.
In addition to uncovering new and potentially worrying findings about antibiotic resistance, the researchers’ work also casts doubt on a long-standing theory about the fitness landscape. These genetic maps show how well an organism – or a part of it, such as a protein – adapts to its environment.

On a fitness landscape, different points on the landscape represent different genotypes of an organism, and the height of these points reflects how well each genotype is adapted to its environment. In the context of evolutionary biology, the goal is to find the highest peak, which indicates the best-fitting genotype.

Prevailing theory regarding fitness landscapes predicts that in extremely rugged landscapes, or those with multiple peaks of fitness, most evolved populations will be trapped at lower peaks and never reach the pinnacle of evolutionary adaptation.

However, testing this theory has been extremely difficult until now due to the lack of experimental data on sufficiently large fitness landscapes.
To address this challenge, Wagner and colleagues used CRISPR gene editing technology to create one of the most combinatorially complete fitness scenarios to date for the E. coli dihydrofolate reductase (DHFR) protein.

What they found was surprising. There were many peaks in the landscape, but most were of low suitability, making them less interesting for adaptation. However, even in this rugged scenario, about 75% of the populations they created reached a high fitness peak, which would give E. coli high antibiotic resistance.

The real-world implications are significant. If such rugged scenarios are common in biological systems, it could mean that many adaptive processes, such as antibiotic resistance, may be more accessible than previously thought.
The results may ultimately lead to re-evaluation of theoretical models in various fields and inspire further research on how real-world scenarios influence evolutionary processes.

“This has profound implications not only in biology but beyond,” says Wagner, “prompting us to reevaluate our understanding of landscape evolution in a variety of fields.” “We need to move from abstract theoretical models to data-informed, realistic scenario models.” (ANI)