E.coli may be far more capable of evolving antibiotic resistance than previously thought, according to a new study.
Scientists say their findings have “profound implications” – not only in biology, but beyond.
A research team experimentally mapped more than 260,000 possible mutations of an E.coli protein that is essential for the potentially deadly bacteria’s survival when exposed to the antibiotic trimethoprim.
Over the course of thousands of “highly realistic” digital simulations, the researchers then found that 75 percent of all possible evolutionary paths of the E.coli protein ultimately endowed the bacteria with such a high level of antibiotic resistance that a doctor would no longer give the antibiotic trimethoprim to a patient.
Study leader Professor Andreas Wagner, an evolutionary biologist at the University of Zurich in Switzerland, said: “In essence, this study suggests that bacteria like E.coli may be more adept at evolving resistance to antibiotics than we initially thought, and this has broader implications for understanding how various systems in evolutionary biology, chemistry, and other fields adapt and evolve.”
Besides uncovering new and potentially worrying findings about antibiotic resistance, the researchers’ work also casts doubt on a longstanding theory about fitness landscapes.
These genetic maps represent how well an organism – or a part of it, such as a protein – adapts to its environment.
On fitness landscapes, different points on the landscape represent different genotypes of an organism, and the height of these points represents how well each genotype is adapted to its environment.
In evolutionary biology terms, the goal is to find the highest peak, which indicates the fittest genotype.
Prevailing theory regarding fitness landscapes predicts that in highly rugged landscapes, or those with multiple peaks of fitness, most evolving populations will become trapped at lower peaks and never reach the pinnacle of evolutionary adaptation.
However, testing the theory has been difficult until now due to the lack of experimental data on sufficiently large fitness landscapes.
Prof Wagner and his colleagues used CRISPR gene editing technology to create one of the most complete fitness landscapes to date for the E.coli dihydrofolate reductase (DHFR) protein.
What they found was surprising as the landscape had many peaks, but most were of low fitness – making them less interesting for adaptation.
However, even in the rugged landscape, about 75 percent of the populations they simulated reached high fitness peaks, which would grant E.coli high antibiotic resistance.
The researchers say that the real-world implications are “significant” as if rugged landscapes are common in biological systems, it could mean that many adaptive processes – such as antibiotic resistance – may be more accessible than previously thought.
The findings, published in the journal Science, could ultimately lead to a re-evaluation of theoretical models in various fields.
Prof Wagner added: “This has profound implications not only in biology but beyond, prompting us to re-evaluate our understanding of landscape evolution across various fields.
“We need to shift from abstract theoretical models to data-informed, realistic landscape models.”
Produced in association with SWNS Talker
