The case of mcr-3 illuminates the complex interplay between antibiotics and the natural environment, which scientists are only just beginning to understand. It makes sense to find resistance genes in hospitals or on farms, where antibiotics are used to treat humans or animals. But why would antibiotic resistance genes turn up in bacteria from the natural environment—even in an isolated cave or 30,000-year-old permafrost? Does the natural environment harbor a reservoir of antibiotic resistance genes, waiting to spring into action?

First, some history about colistin. Decades ago, as colistin fell out of favor for human medicine, farmers started using it. Small doses of antibiotics can fatten pigs and chickens, so colistin became a growth promoter added to feed. China has been a major user of colistin in agriculture, and it’s Chinese scientists who first detected the mcr-1 resistance. But the drug has also been used worldwide in various ways, from promoting growth to preventing and treating diarrheal diseases in animals. (This year, China banned the use of colistin as a growth promoter, and Europe is cutting down on its use in prevention. Treating sick animals with it is still allowed, though.)

Infections resistant to multiple drugs—the kind that might require resorting to colistin—are thankfully still rare, and they’re mostly a concern for the already sick and immunocompromised. But if colistin resistance becomes more common, these patients would lose one of their only remaining options.

So the bombshell discovery of mcr-1 set off a search through bacteria collections around the world. And soon enough, researchers found mcr-1 in dozens of countries, even in decades-old samples of Enterobacteriaceae, a group of bacteria that includes E. coli and Salmonella. The gene had spread around the world before scientists even knew to look for it.

Unfortunately, the same thing has probably already happened with mcr-3. In fact, when Wang and his coauthors went to compare the DNA sequence of mcr-3 to previously sequenced bacteria, they found three 100 percent matches—in Enterobacteriaceae from a Malaysian pig in 2013, human pus in Thailand in 2015, and human stool in the U.S. in 2008.

What makes mcr-3 different from mcr-1 is the existence of mcr-3-like genes in a whole different group of more distantly related water bacteria, the Aeromonas. For example, one bacteria sample from Malaysian lake water had 94.1 percent similarity to the enzyme encoded by mcr-3. And some Aeromonas species seem to have intrinsic resistance to colistin’s class of antibiotics. Wang is now working to isolate the mcr-3-like gene in Aeromonas to figure out if it is indeed what gives the bacteria resistance to colistin.

What could Aeromonas be doing with a colistin-resistance gene out in the environment? This kind of scenario is actually quite common. “Environmental bacteria are just chock full of resistance genes,” says Gerry Wright, a biochemist at McMaster University, who has looked in places like permafrost and isolated caves for resistance genes. One answer could be that bacteria are protecting themselves. Many antibiotics actually come from microbes, which may be creating toxins to fight off their microbe competitors. In fact, colistin was first isolated from a flask of bacteria in Japan.