An international team of scientists reported yesterday that they have detected antibiotic resistance genes in soil from remote group of islands the High Arctic, a finding they say illustrates the global nature of the threat.
Among the genes found by the team was blaNDM-1 (New Delhi metallo beta-lactamase-1), which confers resistance to a broad range of antibiotics and has been associated with highly resistant bacterial pathogens and severe, multidrug-resistant infections.
The blaNDM-1 gene was first discovered in a patient treated at an Indian hospital in 2008 and subsequently in Indian surface waters. Since then, it has spread to hospitals in more than 70 countries.
The genes were found in soil from the Kongsfjorden region of Svalbard, an archipelago in the Arctic Ocean roughly midway between Norway and the North Pole. While many resistance genes have spread around the world, and it's a known fact that antibiotic resistance isn't limited by borders, finding a multidrug-resistance gene in such a remote location, the scientists write, highlights "how rapidly AR [antibiotic resistance] can globalize."
The findings appear in the journal Environment International.
A remote, but not pristine, location
The team, which was led by scientists from the United Kingdom and included researchers from the United States and China, set out to study the soil from Svalbard in 2013 because they thought it would make an ideal location to assess the global spread of resistance genes, which have been found in soil in most places affected by human activity, and have been found in increasing amounts since the discovery of antibiotics in the 1940s.
The island is remote, exposure to antibiotics is minimal, and the temperature is cold enough to preserve soil DNA.
Finding antibiotic resistance genes in remote areas is not new. Resistance genes have previously been found in soil from pristine locations that would not have been exposed to antibiotics, evidence that soil bacteria have been producing defense mechanisms to fend off other bacteria since long before the advent of antibiotics. While Svalbard is remote, it is not pristine: It has no agriculture or industry but does have wildlife and small human settlements, and the waters of Kongsfjorden—an inlet on the west side of Svalbard's main island—don't freeze because of Gulf currents. Wildlife, humans, and open water are all potential sources of antibiotic resistance genes.
By taking soil samples from eight locations around Kongsfjorden—including remote areas at high elevation and those closer to water, wildlife, and the small research town Ny-Ålesun—the scientists thought they might find a mixture of naturally occurring resistance genes and those that have found their way to the islands.
"It gave us a good baseline but also a good representation of a bunch of geochemical environments that we know support native microbial soil communities," study co-author and Kansas University geology professor Jennifer Roberts, PhD, told CIDRAP News. From the point of view of antibiotic resistance, Roberts explained, this included soil "where we might see the most likelihood of transporting new genes into the system."
Once the soil samples were collected and the DNA extracted, the scientists used high-throughput quantitative polymerase chain reaction—a method that amplifies DNA sequences—to identify resistance genes and the mobile genetic elements that can share and spread those genes between bacteria. They also analyzed soil chemistry.
Altogether, they detected 131 antibiotic resistance genes in the soil samples that were associated with resistance to nine antibiotic classes, including aminoglycosides, macrolides, and beta-lactam antibiotics. While resistance genes were found in soil clusters from all eight locations, and blaNDM1 was found in five locations, one site in particular—named SL3, for the small lake located there—had a higher abundance of resistance genes and mobile genetic elements compared to the others.
Different types of resistance genes
The scientists note that some of the resistance genes they identified in the more remote locations were dominated by non-specific resistance mechanisms (such as efflux pumps) that are commonly found in soil microbes and represent evolutionary selection and not necessarily a response to antibiotic exposure. These genes, therefore, were likely naturally produced by soil bacteria in their competition with other bacteria—the type of "background" resistance that's native to any soil.
But the resistance genes found in SL3, including blaNDM-1, were drug-specific, and the abundance of mobile genetic elements in soil from this location suggest they were likely acquired from other bacteria and not locally produced. The scientists note that the high levels of blaNDM-1 at SL3, in fact, were similar to levels found in environments contaminated by wastewater from hospital and other urban sources.
How does an antibiotic resistance gene that originated in India and is found mainly in hospitals get to the High Arctic? Analysis of the soil chemistry suggests different concentrations of nutrients and organic matter at the various sites tell part of the story.
For example, the analysis found much higher levels of phosphate in SL3 than in the more remote sampling sites, most likely attributable to large amounts of fecal matter from High Arctic migratory birds that gather at the site. In contrast, the more remote sites, where fewer antibiotic resistance genes were found and no mobile genetic elements were detected, had low levels of phosphate in the soil.
"What this study showed was a very nice correlation between places where we had an unexpectedly high amount of phosphate that we could tell isn't from the soil and isn't from the native sources associated with these genes, and those two pieces of information together strongly support the hypothesis that these genes are transported in with some kind of waste…and not soil derived," Roberts explained.
Roberts and her colleagues speculate that the birds acquired the resistance genes elsewhere and transmitted them to Svalbard through their feces.
"That is the very basic hypothesis; you have migratory birds who are picking these genes up in open water, or anywhere they've been dispersed, and then depositing them in Svalbard," Roberts said.
Other possible explanations are that Arctic foxes could have acquired the genes from picking through trash around Svalbard's human settlements. Wastewater from a nearby research station is another possible source.
"That's what exciting about this research, trying to use the places in Svalbard, or other places that seem to be still isolated, and then really get more granular about what these pathways for transmission really are," Roberts said.
The global resistance threat
While the resistance genes themselves don't pose a health threat, Roberts says the detection of these genes, particularly one as clinically important as blaNDM-1, in such a remote location with little human activity is worrisome, suggesting that antibiotic resistance has many pathways to spread and is not just a problem in highly populated areas where antibiotic exposure is common.
"It really highlights that this is a global issue that we're going to have to think about relative to human health. If we can get antibiotic resistance genes into our water systems, wherever they are, then they are now in the system, and it can't be a local response—we're going to have to think about it globally," she said. "We've already promoted very rapid antibiotic resistance, and production and evolution of these genes, in very populated locations…so we need to stop or change what we're doing in those areas, but it also means we can't assume that it's confined to those areas."
Roberts also noted that the findings could have increased significance because of climate change.
"If we continue to see the widespread thawing in these places that we think of as more remote, then as thawing goes on and warming continues, the trajectory of course is toward there being pathogens that can persist in these water bodies," she said. "If we have thawing and populations spreading northward, then certainly that becomes an issue.
Jan 28 Environ Int study