The spread of antibiotic resistance, a growing threat to global health that causes millions of deaths annually, is typically blamed on the overuse of drugs in hospitals and in the food industry. However, a new study published in Nature Microbiology suggests that normal geological processes could be accelerating the development of new resistances.
Soil microorganisms naturally produce antibiotics as a form of chemical warfare to compete with each other. When soils dry out, these natural compounds become more concentrated because there is less water to dilute them. Like a dosage increase, this concentration can create a harsher environment, killing sensitive microbes and sparing those with the capacity to resist. This phenomenon, in turn, is an evolutive driver that favors the appearance of new and more effective resistance genes.
“If you have more antibiotics in your environment, only the organisms that can withstand it…can resist it.”
To test whether this mechanism is having real genetic effects, Xiaoyu Shan, a microbial ecologist and postdoctoral researcher at the California Institute of Technology (Caltech), and colleagues looked at soil samples under controlled conditions as the samples transitioned from a wet state to a desiccated one. They found that as the soil dried, the presence of genes related to antibiotic production and resistance spiked, suggesting that drought leads to a rapid escalation in the subterranean biological arms race. Importantly, they did not look for pathogenic bacteria specifically, only for resistance genes, which can be present in a variety of microbes, whether those microbes are pathogenic or not.
“Drought leads to this elevation of antibiotic producers and bacteria that are resistant,” said team member Dianne Newman, a professor of biology and geobiology also at Caltech. “It’s a pretty simple idea: If you have more antibiotics in your environment, only the organisms that can withstand it…can resist it.”
Alternative Explanations
However, there could be other potential explanations for the observed increase in antibiotic-producing and antibiotic resistance genes, according to Enrique Monte, a microbiologist at the Universidad de Salamanca in Spain who wasn’t involved with the new study. For instance, arid soils are naturally more diverse than humid soils, making it common to find a more diverse gene pool in the ground, Monte said. In addition, the mere presence of antibiotic genes might not result in an actual release to the environment, or a release could happen in dosages that are too small to cause noticeable effects. “There are antibiotics that are volatile; they escape into the air, so they never reach a therapeutic concentration to kill others,” Monte said.
The authors, however, took some precautions to show that the increase in antibiotic resistance genes was actually a biological response to environmental stress. For instance, they also tracked other genes that should remain unaffected or decline under desiccation. As expected, genes that are needed for basic survival remained stable, while genes responsible for bacterial movement declined in dry soil, where mobility is restricted. Even some species that were not favored by desiccation saw an increase in resistance-related genes, “which is even stronger evidence,” Shan said.
Geographic Limitations
As the researchers combed through publicly available metagenomic data libraries, they had to select collections with strict control of all variables and in which the only changing factor was water content. That limited the analysis to five locations: two grasslands and a sorghum field in California; a forest in Valais, Switzerland; and a wetland in Nanchang, China.
The scarcity of locations might limit how extrapolable these results are, said Fiona Walsh, a microbiologist at Maynooth University in Ireland who was not involved with the work. “There are thousands of high-quality metagenomes available online with excellent metadata. I would really like to see a comparison where they apply their analysis to a broader map of global metagenomic data to see if they reach the same conclusions,” she said.
From the Soil to the Hospital
Drier regions consistently showed a higher number of resistant bacteria cases in hospitals, even after adjusting for confounding factors such as local income.
The study also suggests that dry soils might be a hidden driver of clinical cases of antibiotic resistance worldwide. The authors combined hospital data on the number of cases of resistant infections from 116 countries with the local aridity index, which measures temperature and precipitation, for each location. They found a strong correlation: Drier regions consistently showed a higher number of resistant bacteria cases in hospitals, even after adjusting for confounding factors such as local income.
However, the authors admitted that this is only a correlation effect and doesn’t prove causation. “It motivates follow-up research to see how environmental concentration weighs against human overuse and poor stewardship,” Newman said.
Even this correlation could be a stretch, according to microbiologist Sara Soto, head of the Global Viral and Bacterial Infections Programme at the Instituto de Salud Global de Barcelona. At the end of the day, she said, the authors have soil data from only five locations in three countries, and they are not tracking the specific bacterial varieties that make people sick, only resistance genes.
For the thesis to be solid, Soto said, the ideal approach would have been to contrast hospital strains from a specific area with soil data from that same region during the same drought episode. “Making such a vast inference—that what happens in the soil of one location affects what happens in a hospital elsewhere—is a big leap,” she said.
The authors, however, point out that resistance genes from soils can eventually make their way into human pathogens. Microbes have the capacity to share genetic material across species—a process known as horizontal gene transfer. In their analysis, the team identified specific resistance sequences that appeared to have been transferred between soil bacteria relatively recently, perhaps within the past decade. How they are reaching hospitals remains a matter for a future study, they said.
As droughts increase in numerous regions in the face of climate change, this selective pressure within soil ecosystems is expected to intensify. Though these findings do not show that drought directly puts drug-resistant pathogens in hospitals, they still suggest that a drying climate could set the scene for an increase in antibiotic resistance, the researchers report.
—Javier Barbuzano (@javibar.bsky.social), Science Writer