“There is ample evidence to suggest that human pathogens acquire their antimicrobial resistance (AMR) through other species living in the natural environment,” said senior author Lingchong You, a professor of biomedical engineering at Duke. “Intuitively, it makes sense that high levels of antibiotics in these environments make it easier for resistance genes to jump from chromosomes to plasmids so they can spread, but the underlying mechanism has never been unraveled.”
The increase in resistance coincides with the increase in the use of antibiotics.
Although resistance genes appear to be relatively new for these pathogens, it is very likely that human pathogens have acquired these resistance genes through the environment due to increased environmental levels of antibiotics. Although cause and effect seem clear, research has never been able to establish the underlying mechanisms.
It all starts with plasmids, small floating bits of DNA carry resistance genes between cells. However, several studies have shown that the presence of antibiotics does not increase the rate at which plasmids carry out these gene exchanges. What then can be the vector that animates this natural selection? Scientists here invoke an antibiotic-mediated selection process on “jumping genes,” or “transposons,” which carry resistance genes from the cell’s chromosomes to plasmids.
The role of transposons: Experiments designed to better understand the role of transposons confirm and shed light on how different pathogens acquire resistance from species present in the environment: transposons, small bits of DNA, are constantly jumping around in the central genetic database of the cell and then change from DNA to plasmids capable of traveling between cells and vice versa. The result of these jumps and trips are chromosomes or plasmids that contain many copies of the same genetic blueprints that confer multiplied resistance to different types of antibiotics. As the concentration of antibiotics increases, bacterial cells carry plasmids with more copies of resistance genes.
More antibiotics, more copies of resistance genes: the 2 curves for antibiotic concentration and resistance gene copy number are nearly similar, the researchers write. And the number of copies of transposons on the plasmids affects how many antibiotic-resistant proteins the cell makes.
What trigger threshold? According to the researchers, the levels or thresholds of antibiotics needed to trigger this selection and resistance process vary considerably from one antimicrobial to another. but they write that “These levels are not uncommon in our current natural environments, which therefore present the pressure necessary to induce human pathogens to detect the resistance genes present.”
The next step will be to reproduce this resistance “cascade” in real life, in real settings like hospitals, for example, and not just in a Petri dish.