Info Service on Health Issues (Mar15/02)
Study Links Widely Used Pesticides to Antibiotic Resistance
Further to our mailout of yesterday (‘Exposure to herbicides can cause change in bacterial response to antibiotics’, BIS 25 March 2015), please find below two news articles on the issue of antibiotic resistance and the links to commercial formulations of the herbicides glyphosate, 2,4-D and dicamba.
Glyphosate, 2,4-D, and dicamba found to affect bacteria in ways that could promote resistance to common antibiotics.
This has not been a good week for glyphosate, the active ingredient in Roundup and other herbicides. On Friday, the World Health Organization (WHO) announced that it had classified glyphosate, the United States’ most widely-used pesticide, as “probably carcinogenic to humans.”
Now, the chemical has another strike against it. A study published today by the American Society of Microbiology’s journal mBio has linked glyphosate and two other widely-used herbicides–2,4-D and dicamba–to one of the most pressing public health crises of our time: antibiotic resistance.
This study found that exposure to these herbicides in their commercial forms changed the way bacteria responded to a number of antibiotics, including ampicillin, ciprofloxacin, and tetracycline–drugs widely used to treat a range of deadly diseases.
Dicamba, 2,4-D, and glyphosate have been in use for decades, so why have their antibacterial-resistance effects not been documented before? As the study’s lead author, Jack Heinemann, professor of genetics at the University of Canterbury in New Zealand, explains, when pesticides are tested for adverse effects, “it’s the lethal toxicity that people focus on.” In other words, how much of the chemical will kill an organism.
“What makes our study different, is that it is looking at a sub-lethal effect,” says Heinemann. “The effect we see requires that the bacteria stay alive.”
Previous studies done by other researchers have found that substances chemically similar to dicamba and 2,4-D can cause antibiotic resistance, Heinemann explains. So he and his colleagues decided to investigate whether these herbicides would produce similar effects. They added glyphosate to the study because it is chemically unlike the other two. But, to their surprise, it also produced some antibiotic resistance.
Heinemann explains that because these herbicides are not “supertoxic” to the bacteria the study tested–E. coli and Salmonella–they are not killed outright at levels typically used to kill weeds. Instead, the bacteria stay alive while activating proteins known as efflux pumps in order to rid themselves of toxins. And this defense mechanism can make the bacteria develop resistance to the threat from which it is defending itself.
Scientists know that overuse of antibiotics in humans can decrease their effectiveness. In the same way, says Heinemann, “exposure to these pesticides make the pathogens stronger.”
Although this study only looked at two laboratory strains of human pathogens, the antibiotics examined represent what he calls “broad classes” of drugs we’ve come to depend on to fight infections and the herbicides are three of the most-used worldwide.
Heinemann also notes that the different pesticides produced a variety of responses. While all three produced an antibacterial-resistant response to some of the antibiotics, some of the combinations his team tested produced no response and some increased the antibiotic’s effect.
Although the study is likely to be seen as controversial by some, University of Massachusetts Dartmouth assistant professor of biology, Dr. Mark Silby says it “followed established protocols” and the existing scientific literature supports its findings.
“This is a very carefully-designed study,” says Dr. Michael Hansen, a senior staff scientist at Consumers Union. “It’s incredibly important work showing the complexity of an effect that hadn’t been thought about before.” The mechanisms by which the bacteria respond to toxics–in this case herbicides–are already well-known, Hansen explains. What’s new and important is looking at non-lethal levels of exposure in combination with the antibiotics.
The weed-killers used in the study were purchased at a local store and were used at levels specified in use directions, which means the scientists were testing chemicals actually in use worldwide rather than a special laboratory sample of the active compound.
could any of this affect people?
The levels at which the researchers saw effects were higher than the residues allowed on food, but below what is often used in rural settings, says Heinemann.
The results of Heinemann’s study suggest there is probably a small chance that exposure through food would produce these effects, but they could be a concern in areas where the pesticides are being applied, says Hansen. Thus, the people most likely to be affected are farmers, farmworkers, and other people who live in agricultural communities.
Also to consider is the approval earlier this year of a new pesticide that combines glyphosate and 2,4-D and soybean and cotton seeds genetically engineered to resist dicamba, all of which are expected to increase use of these pesticides.
Pesticide-induced antibiotic resistance could also affect honeybees since many commercial hives are now being treated with antibiotics. It’s possible, Heinemann says, that “comingling of antibiotics and herbicides could be compromising the effectiveness of those antibiotics,” and thus honeybee health.
Meanwhile, Monsanto says it disagrees with WHO’s announcement on glyphosate. “All labeled uses of glyphosate are safe for human health and supported by one of the most extensive worldwide human health databases ever compiled on an agricultural product,” the company says in a statement on its website.
Neither Monsanto nor other pesticide manufacturers have had the opportunity to respond to the new mBio study. But the Council for Biotechnology Information said on its website “GMO Answers” last month, that glyphosate had once been considered for use as an antibiotic but that “levels needed to kill microbes are relatively high, and resistance can develop readily.” In other words, the phenomenon Heinemann and colleagues observed is not entirely unexpected.
“A jigsaw puzzle is a good metaphor,” for how these effects fit together, says the scientist.
The next steps in this research will be to test additional bacteria and pure samples of the pesticides. But for now, it’s clear that “further work is needed,” says Hansen. “This is something we need to look at as we expand the use of these herbicides.”
Common pesticides linked to antibiotic resistance
People exposed to herbicides require more antibiotics to kill bacteria, according to new research published in mBio
Antibiotics and herbicides, as it turns out, don’t mix. At least that’s the conclusion of a study published today in mBio, the peer-reviewed journal of the American Society for Microbiology, which found that if someone is exposed to both herbicides and antibiotics at the same time, higher doses of antibiotics will likely be needed to kill the offending bacteria.
It’s the first study of the effect of herbicides on antibiotics, and its findings could have implications for antibiotics resistance. The growing risk of disease from antibiotic-resistant pathogens is a huge public health concern, one that was recently prioritized by both the World Health Organization and the US Centers for Disease Control.
According to Jack Heinemann, the study’s lead author, policy makers and researchers should look at multiple factors, not just over-use of antibiotics, in fighting antibiotics resistance. In addition, as more genetically modified crops are planted, use of herbicides is expected to increase.
“The countries that are growing GM crops at scale may wish to include these unanticipated effects on microbes in their evaluations,” Heinemann said.
The study comes a week after glyphosate, an agricultural herbicide produced by Monsanto and more commonly known as RoundUp, was deemed “probably carcinogenic” by the World Health Organization.
The level of herbicide exposure tested in the mBio research was higher than what would generally be found as residue on food, but lower than application standards for commercially available herbicides.
The level is compatible with the amount that people in rural areas can be exposed to from herbicide drift – the wind distributing chemicals sprayed in one field across many other plots of land – and what urban dwellers might be exposed to from using herbicides in their own or their neighbors’ gardens.
“The exposure pathways that we identified as possibly being the most relevant for future study generally arose from the use of the herbicide by others – for example, in the urban setting” Heinemann said. “Therefore, it may take communities talking to each other to find ways to reduce unintended exposures.”
Heinemann and his fellow researchers tested various combinations of three of the most commonly used herbicides: dicamba (sold commercially under the name Kamba); 2,4-dichlorophenoxyacetic acid; and glyphosate (RoundUp). They also studied five different classes of antibiotics: ampicillin, ciprofloxacin, chloramphenicol, kanamycin, and tetracycline.
In some cases, certain combinations of herbicide and antibiotic either improved the performance of the antibiotic or had no effect on the antibiotic at all. But in the majority of cases, the herbicide made the antibiotic less effective.
More research, though, is needed, and agrichemical producer Monsanto is in agreement with Heinemann over what needs to be studied next: whether or not it’s the active ingredient of these herbicides that affects antibiotics.
“It is difficult to separate the effect of surfactants, which are known to have an impact on cultured microbes, from the active ingredients,” said Charla Lord, a spokesperson for Monsanto.
From Heinemann: “We are particularly interested in determining whether these effects are caused by the stated active ingredient of the herbicides (glyphosate, dicamba and 2,4-D) or by other compounds that make up the commercial formulation.”
If it turns out to be the inactive ingredients that reduce the potency of antibiotics, that could implicate a wider range of herbicides, as several available products have different active ingredients but the same inactive ingredients.
“If the effect [of antibiotic resistance] is largely caused by exposure to the commercial formulation rather than the active ingredient alone, then that will be relevant information for further environment or human health studies,” Heinemann said.
His team also wants to explore exposure pathways to determine which may be most relevant to human health, pet health, and the health of farm animals and important pollinators (honey bees, for example).
In the meantime, the study revealed enough data for Heinemann to conclude that the current practice of testing herbicides in isolation (not in combination with other herbicides, antibiotics or other chemicals that are common in the environment) – which is how governments and companies currently evaluate herbicide risks – “may underestimate [their] role in the emergence of antibiotic resistance”.