What does dry soil like in this part of South Africa have to do with antimicrobial resistance? A new study offers an unexpected hypothesis: Drought could lead to higher antibiotic resistance in soil bacteria.
ROGER BOSCH/AFP/via Getty Images
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ROGER BOSCH/AFP/via Getty Images
It’s one of the highest-stakes battles on Earth: bacteria versus antibiotics.
And bacteria appear to be taking hold in the human realm. Around the world, many antibiotics are beginning to lose their effectiveness. About this 1 in 6 human infections Antibiotics tested in laboratories are resistant, causing more than 4 million deaths per year.
Researchers know that human use, and especially excessive use, has given bacteria the opportunity to develop resistance. But antibiotics, and resistance to them, are much older than the pills we take for infections. Both are the result of one of the longest running battles on Earth, taking place in the soil.
“In nature, organisms are duking it out, it’s a competitive environment,” says diane newmanA microbiologist at Cal Tech. “One of the strategies that microbes have evolved to compete effectively is to produce antibiotics, killing their neighbors.”
This evolutionary arms race has been going on for millennia. But this only really matters to humans since we discovered antibiotics in soil and began using them to treat infections in the 1940s. Newman wondered whether environmental changes in the ultimate source of antibiotics – soil – might also be contributing to this increase.
Drought, it turns out, can Promote high antibiotic resistance In soil bacteria, Newman and colleagues report nature microbiology. Researchers found that this resistance is also working in human infections.
“This is an amazing paper, and shows that drought is already having an impact on health care systems around the world,” says Timothy GhalyA microbial ecologist at Macquarie University in Australia who was not involved in the study. “As drought increases in many parts of the world, this is also likely to increase the spread of antimicrobial resistance.”
looking at the soil
Drought may seem an unlikely candidate for a major factor in antibiotic resistance. But Newman hypothesized that when the soil dried out, the antibiotic bacteria used to wage war might become more powerful, simply because of evaporation.
“Imagine you have a vessel of liquid and a certain amount of antibiotics in it,” says Newman. If you evaporate that liquid, those molecules will remain there, and they will become more concentrated.
It can effectively expose bacteria to high concentrations. “Wherever you increase exposure to antibiotics, you will select for microbes that can withstand them,” she says.
To see if this might be the case, researchers analyzed soil samples taken from around the world. They found that drier soil contained more genes for making antibiotics. The longer the drought conditions, the more genes they found to make antibiotics, which are produced by many types of different bacteria.
“We predicted that as soon as desiccation occurs, you concentrate these antibiotics, and the organisms that survive are able to withstand them,” Newman says. Lab experiments supported this.
The team then re-analyzed those soil samples from around the world, looking for antibiotic resistance genes. They found more of these in dry samples.
“This is novel in terms of presenting a very specific pathway in which drought resistance is increasing the concentration of genes,” says Ramanan LaxminarayanAn epidemiologist at Princeton University, who was not involved in the study. This is a threat, he says, but it doesn’t necessarily translate into a risk for us, unless these resistance genes find their way into human pathogens.
The authors provide evidence of this, but there is controversy over how big a problem this may be.
Penetration into humans?
Most soil bacteria are not human pathogens. But bacteria can swap genes with their neighbors in the dirt – a process known as horizontal gene transfer.
“That’s what allows rapid spread from soil to the clinical setting where it becomes really problematic,” Newman says. His team found that many of the resistance genes associated with drought-stricken soils were also found in bacteria samples taken from people in hospitals. One resistance gene was 100% identical, suggesting relatively recent variation.
It is unclear how these soil resistance genes evolve into human pathogens. Injuries to the knee during a trail run or while gardening provide opportunities for such a transfer, she says. “Wherever we go, we will encounter germs of various forms.”
If such transfers were not extremely rare events, you might expect there to be more antibiotic-resistant infections in areas with dry soils. Newman and colleagues analyzed data on resistance in hospitals in 116 countries, and looked at whether there was an association between resistance and dryness. He found one – the drier the soil, the greater the resistance.
This happens more often in low-income countries high rate of resistance Due to reasons such as lack of clean water and sanitation and less effective infection control in health care systems. The researchers reran the analysis looking only at high-income countries and found that although overall resistance in hospitals was lower, the level of resistance was still strongly associated with dryness.
“It’s very compelling,” Ghaly says. “The correlation was really strong, which is rare to see in biology.”
Other scientists are not convinced.
“That’s a long shot,” says Lakshminarayan. “There are a lot of things that determine resistance in hospitals, like the fact that health care systems are not necessarily good in places where there are drought conditions.” He says more research will be needed to find out whether drought is actually causing an increase in resistant infections.
Nevertheless, Laxminarayan buys the rest of the report.
“This provides evidence that these levels of resistance are changing in the ambient environment, completely unbeknownst to us,” he says. “At some point, it becomes a risk when it’s transferred to domestic animals or livestock or humans.”
To prevent that from happening, he says researchers need to pay more attention to what’s happening in the dirt below.
