It's one of the highest-stakes battles on earth: bacteria versus antibiotics.
And in the human realm, bacteria appear to be gaining ground. Worldwide, many antibiotics are starting to lose their bite. About 1 in 6 human infections tested in labs are resistant to antibiotics, contributing to over 4 million deaths a year.
Researchers know that human use, and especially overuse, have given bacteria opportunities to develop resistance. But antibiotics, and resistance to them, are much older than the pills we pop for infections. Both are the product of one of the longest-running battles on Earth, playing out in soil.
"In nature, organisms are duking it out, it's a competitive environment," says Dianne Newman, a microbiologist at Cal Tech. "One of the strategies microbes have evolved to effectively compete is to produce antibiotics, to kill their neighbors."
This evolutionary arms race has been ongoing for millenia. But it's only really mattered for humans since we discovered antibiotics in soil, and started using them to treat infections in the 1940s. Newman wondered whether environmental changes to the ultimate source of antibiotics — soil — might be contributing to this rise, too.
Drought, it turns out, can drive higher antibiotic resistance in soil bacteria, Newman and her colleagues report in Nature Microbiology. That resistance may be working its way into human infections too, the researchers found.
"It's an awesome paper, and shows that drought is already having an impact on health care systems around the world," says Timothy Ghaly, a microbial ecologist at Macquarie University in Australia who wasn't involved in the study. "With drought increasing in many parts of the world, that's likely to increase the prevalence of antimicrobial resistance as well."
Looking to the soil
Drought may seem an unlikely candidate for a major driver of antibiotic resistance. But Newman had a hunch that when soil dries up, the antibiotics bacteria use to wage war might become more potent, simply because of evaporation.
"Imagine you have a vat of a liquid and you have a certain amount of antibiotics in it," says Newman."If you were to evaporate that liquid, those molecules would stay there, and they would become more concentrated."
That could expose bacteria to higher doses, effectively. "Anywhere you increase exposure to antibiotics, you will select for microbes that can withstand them," she says.
To see if this might be the case, the researchers analyzed soil samples taken from around the globe. They found that drier soils tended to house more genes for making antibiotics. The longer the drought conditions, the more antibiotic-making genes they found, produced by many kinds of different bacteria.
"We predicted that as desiccation happens, you concentrate these antibiotics, and what remains are the organisms that are able to withstand them," says Newman. Lab experiments backed that up.
The team then re-analyzed those soil samples from around the globe, looking for antibiotic resistance genes. They found more of them in drier samples.
"This is novel in terms of positing a very specific pathway in which drought is driving the concentration of resistance genes," says Ramanan Laxminarayan, an epidemiologist at Princeton University who wasn't involved in the study. That's a hazard, he says, but doesn't necessarily translate into a risk for us unless these resistance genes find their way into human pathogens.
The authors provide evidence it can, but just how big a problem that could be is contested.
Getting into humans?
Most soil bacteria aren't human pathogens. But bacteria can swap genes with their neighbors in the dirt – a process known as horizontal gene transfer.
"This is what allows sort of rapid propagation from the soil into the clinical setting where it becomes really problematic," says Newman. Her team found several of the resistance genes associated with drought-stricken soils also popped up in samples of bacteria taken from people in hospitals. One resistance gene was 100% identical, suggesting a relatively recent swap.
It's unclear how these soil resistance genes wound up in human pathogens. Scraping a knee falling on a trail run, or a cut while gardening offer the opportunity for such a transfer to happen, she says. "Everywhere we go, we're going to be encountering microbes of different forms."
If such transfers aren't extremely rare events, you might expect areas with drier soils to have more antibiotic-resistant infections. Newman and her colleagues analyzed data on resistance in hospitals across 116 countries, and looked to see if there was a correlation between resistance and aridity. They found one — the drier the soils, the higher the resistance.
Lower-income countries often have higher rates of resistance for reasons such as lack of clean water and sanitation and less effective infection control in healthcare systems. The researchers re-ran the analysis, looking only at high-income countries, and found that while there was less overall resistance in hospitals, resistance levels were still strongly correlated with aridity.
"It's very compelling," says Ghaly. "The correlation was really strong, which is rare to see in biology."
Other scientists aren't convinced.
"That's a stretch too far," says Laxminarayan. "There are so many things that determine resistance in hospitals like the fact that health care systems might not necessarily be great in places that have drought conditions." He says more research would be needed to nail down whether drought is actually causing an uptick in resistant infections.
Still, Laxminarayan buys the rest of the report.
"It adds to evidence that these levels of resistance may be changing in the ambient environment, just completely unbeknownst to us," he says. "At some point, it becomes a risk when it transfers into domestic animals or to livestock or to humans."
To prevent that from happening, he says researchers may have to pay closer attention to what's going on down in the dirt.
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