Danish researchers are proposing a fundamental shift in how scientists understand antibiotic resistance, arguing that whether a bacterium actually behaves as resistant depends heavily on the environment it's in—not simply whether it carries a resistance gene.
In their opinion piece, published in Trends in Microbiology, argue that the traditional binary view of resistance—where a laboratory test declares a bacterium either susceptible or resistant to a given antibiotic—may no longer hold up. That framework has long shaped how infections are diagnosed, how patients are treated and how resistance is monitored in humans, animals, food and the environment worldwide. But recent research from the DTU National Food Institute found that factors such as temperature, oxygen levels and pH can significantly affect whether a bacterium carrying a resistance gene actually behaves in a resistant manner.
Two supporting studies underpin the opinion piece: one found that two different beta-lactamase enzymes, CTX-M and CMY, have contrasting pH optima that influence how E. coli fitness and resistance play out, while the other found that pH and redox potential modulate beta-lactam resistance more broadly.
Current standard laboratory tests don't account for whether a bacterium is sitting in the oxygen-free environment of the gut or the oxygen-rich bloodstream, or whether a patient has a fever—conditions the researchers say could determine whether a resistance gene actually confers resistance in practice.
This new understanding may help to explain why a course of antibiotics sometimes fails to work, even though laboratory tests show that it ought to, or vice versa. If resistance depends to a large extent on the bacteria’s environment, this also opens up the possibility of entirely new ways of thinking about combating antibiotic resistance.
“Now that it has been shown that a bacterium’s resistance depends on its environment, the next step will be for us to choose to use antibiotics that only lead to the development of resistance if certain specific conditions are met. This could, for example, be at a particularly high temperature that does not occur in humans,” said opinion author Frank Møller Aarestrup, professor at the DTU National Food Institute. “We can start to consider entirely new strategies for combating antibiotic resistance in humans, animals and the environment.”
Data from Technical University of Denmark