Toxic to Tasty
Broad Range of Antibiotics Found to Nourish Hundreds of Bacterial Strains
When a team of HMS geneticists broke out their spades to collect soil samples for a U.S. Department of Energy project called Genomes to Life, they were looking for genetic diversity. The project aimed to speed the conversion of biomass into biofuels and hinged on a hunt for the molecular machinery to do it. The researchers, led by George Church, HMS professor of genetics, found more than they had bargained for.
The first hints that they were on to something unexpected came when they were designing control environments for the biofuels project. To stop biomass conversion, they added antibiotics to the soil, expecting the drugs to kill the microorganisms.
“We were blown away to find that everything we looked at—and with every antibiotic we tried in the experiment—was growing on these antibiotics without a problem,” said Gautam Dantas, HMS research fellow in genetics. “We said, wait a minute. This is not a control experiment. This is the experiment.”
This observation sent co–first authors Dantas and Morten O. A. Sommer, a Harvard biophysics doctoral candidate, on a digging expedition. They suspected that microorganisms from soils with more exposure to antibiotics from human and animal use might show more of an ability to subsist on antibiotics, so they gathered a variety of samples. They collected agricultural samples from Carlisle, Mass., and Pelican Rapids, Minn. Urban soils came from the Boston Fens and Public Garden. Pristine soils were trickier. One sample came from an island in Pennsylvania bounded by lumber companies on opposing riverbanks. In a corporate standoff, both deemed the island off limits, leaving it untouched for a century.
With 11 soil samples in hand, the researchers tested each against 18 clinically relevant antibiotics. They found more than 600 different strains of bacteria across the samples that were able to live on antibiotics as their sole food source. They found no statistically significant differences between the soils (see figure). The results appear in the April 4 Science.
Antibiotics Lose Their Luster
The Church team’s results extend both the breadth and depth of this antibiotic resistome. Dantas and Sommer randomly selected 75 strains from the 600-plus they had found and tested them for antibiotic resistance. These 75 bacteria on average were resistant to between 17 and 18 of the 18 antibiotics tested. Moreover, a phylogenetic mapping of these strains shows that the antibiotic resistome spans many different orders of bacteria, including several orders containing human pathogens.
“This shows that there is a tremendous amount of genetic diversity out there,” said Wright. In addition, “this tells us that antibiotics are not that special.” Though to humans, antibiotics may be “wonder drugs,”—and in fact, life expectancy rates have climbed by 20 years since the first antibiotics were prescribed in the 1930s—“the reality is they are just regular organic molecules.”
While antibiotics may be just another food source, bacteria also happen to be excellent scavengers. Church, Dantas, and Sommer speculate that this ability to scavenge does not come from genes specialized to metabolize individual drugs, such as penicillin or ciprofloxacin. Rather, said Dantas, these scavengers have an “extremely plastic metabolism” that is able to recognize and “chew off” small bits of organic molecules. This flexible genetic machinery allows them to survive in environments where carbon sources are scarce.
Though the underlying mechanisms of super-resistance are not yet known, Church said, “organisms that are eating antibiotics are probably special in some way.” For instance, they may be combining multiple resistance strategies to disarm and degrade the antibiotic.
“The really exciting part of what’s next is that we have the capacity to understand these mechanisms,” said Wright.
But there is also an alarming aspect. Human pathogens might pick up these
abilities to resist antibiotics through gene transference, said Sommer, because “the
mechanisms that are used to transfer resistance genes tend to work better
when you’re closely related.” Nearly three quarters of the 75
isolated strains were members of orders that contain human pathogens such
as Salmonella, Escherichia coli, and bacteria that cause pneumonia. Moreover,
antibiotic pollution in the soil from human and animal use may add selective
pressure that favors bacteria that can subsist on these clinically important
Church is more focused on the possibilities that the antibiotic resistome opens up for using synthetic biology to design organisms that eat toxins. “Bioremediation can be a way to clean up the soil from antibiotics and other chemicals,” said Church. “You just want to do it safely, so whatever organisms you’re using to clean up the toxic waste dump don’t themselves become a pest.”
Church’s lab is working on a safe “chassis” for such synthetic life, though completion is likely several years out.
In the meantime, Church, Dantas, and Sommer intend to investigate some of the more immediate questions that their study has raised. They want to identify the genes behind antibiotic resistance and subsistence and understand their transfer patterns and metabolic biochemistry. “It’s exciting that there is so much to do,” said Dantas, “but it also means there are 600 starting points for every experiment.”