THIRD WORLD NETWORK BIOSAFETY INFORMATION SERVICE
Dear Friends and Colleagues
Exposure to herbicides can cause change in bacterial response to antibiotics
The issue of antibiotic resistance has been gaining increasing political attention worldwide because of the major risks to human health, due to the potential compromise in therapy.
A new study published today demonstrates that sub-lethal exposure to the herbicides dicamba, 2,4-D and glyphosate can cause bacteria to change their response to clinically-relevant antibiotics. They often become antibiotic-resistant, but the researchers also saw increased susceptibility or no effect. The response was only observed in the presence of both the antibiotic and herbicide.
Glyphosate is the world’s most commonly used herbicide, whose use has risen with the development of genetically modified (GM) crops made resistant to it. Due to increasing problems with resistance development in weeds, biotech companies have now developed GM crops resistant to other herbicides, such as dicamba and 2,4-D.
The implications of the widespread use of these herbicides (also in conjunction with herbicide-resistant GM crops), and their potential interaction with antibiotics have not been previously considered in risk assessments.
The paper is available at http://mbio.asm.org/content/6/2/e00009-15
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Item 1
Sublethal Exposure to Commercial Formulations of the Herbicides Dicamba, 2,4-Dichlorophenoxyacetic Acid, and Glyphosate Cause Changes in Antibiotic Susceptibility in Escherichia coli and Salmonella enterica serovar Typhimurium
Brigitta Kurenbach, Delphine Marjoshi, Carlos F. Amábile-Cuevas, Gayle C. Ferguson, William Godsoe, Paddy Gibson, Jack A. Heinemann
ABSTRACT
Biocides, such as herbicides, are routinely tested for toxicity but not for sublethal effects on microbes. Many biocides are known to induce an adaptive multiple-antibiotic resistance phenotype. This can be due to either an increase in the expression of efflux pumps, a reduced synthesis of outer membrane porins, or both. Exposures of Escherichia coli and Salmonella enterica serovar Typhimurium to commercial formulations of three herbicides— dicamba (Kamba), 2,4-dichlorophenoxyacetic acid (2,4- D), and glyphosate (Roundup)—were found to induce a changed response to antibiotics. Killing curves in the presence and absence of sublethal herbicide concentrations showed that the directions and the magnitudes of responses varied by herbicide, antibiotic, and species. When induced, MICs of antibiotics of five different classes changed up to 6-fold. In some cases the MIC increased, and in others it decreased. Herbicide concentrations needed to invoke the maximal response were above current food maximum residue levels but within application levels for all herbicides. Compounds that could cause induction had additive effects in combination. The role of soxS, an inducer of the AcrAB efflux pump, was tested in [beta]-galactosidase assays with soxS- lacZ fusion strains of E. coli. Dicamba was a moderate inducer of the sox regulon. Growth assays with Phe-Arg [beta]-naphtylamide (PA[beta]N), an efflux pump inhibitor, confirmed a significant role of efflux in the increased tolerance of E. coli to chloramphenicol in the presence of dicamba and to kanamycin in the presence of glyphosate. Pathways of exposure with relevance to the health of humans, domestic animals, and critical insects are discussed.
IMPORTANCE
Increasingly common chemicals used in agriculture, domestic gardens, and public places can induce a multiple-antibiotic resistance phenotype in potential pathogens. The effect occurs upon simultaneous exposure to antibiotics and is faster than the lethal effect of antibiotics. The magnitude of the induced response may undermine antibiotic therapy and substantially increase the probability of spontaneous mutation to higher levels of resistance. The combination of high use of both herbicides and antibiotics in proximity to farm animals and important insects, such as honeybees, might also compromise their therapeutic effects and drive greater use of antibiotics. To address the crisis of antibiotic resistance requires broadening our view of environmental contributors to the evolution of resistance.
Citation Kurenbach B, Marjoshi D, Amábile-Cuevas CF, Ferguson GC, Godsoe W, Gibson P, Heinemann JA. 2015. Sublethal exposure to commercial formulations of the
herbicides dicamba, 2,4-dichlorophenoxyacetic acid, and glyphosate cause changes in antibiotic susceptibility in Escherichia coli and Salmonella enterica serovar Typhimurium. mBio 6(2):e00009-15. doi:10.1128/mBio.00009-15.
Item 2
Q & A for Sub-lethal exposure to commercial formulations of the herbicides dicamba, 2,4-D and glyphosate cause changes in antibiotic susceptibility in Escherichia coli and Salmonella enterica serovar Typhimurium by Brigitta Kurenbach, Delphine Marjoshi, Carlos F. Amábile-Cuevas, Gayle C. Ferguson, William Godsoe, Paddy Gibson and Jack A. Heinemann
What did you find?
We found that exposure to some very common herbicides can cause bacteria to change their response to antibiotics. They often become antibiotic resistant, but we also saw increased susceptibility or no effect.
The direction or magnitude of the observed effects were not predictable from the bacterial species, antibiotic or herbicide used.
The effects found are relevant wherever people or animals are exposed to herbicides at the range of concentrations achieved where they are applied. This may include, for example, farm animals and pollinators in rural areas and potentially children and pets in urban areas. The effects were detectable only at herbicide concentrations that were above currently allowed residue levels on food.
Which herbicides did you use in your study?
We used commercial formulations of Kamba (dicamba), 2,4-D and Roundup (glyphosate).
Is this the first study to show this?
To our knowledge, yes. Other substances have been shown to change bacteria’s tolerance to antibiotics (e.g. aspirin), but herbicides were never tested.
Why does it matter?
Antibiotic resistance is a problem for human and animal health.
New antibiotics are hard to find and can take decades to become available.
Effects of chemicals such as herbicides could conflict with measures taken to slow the spread of antibiotic resistance.
Additional information:
There are more individual antibiotics than we could test in our study. However, we tested examples from most major groups of antibiotics.
We only tested 2 bacterial species. Both were common laboratory strains of species that can cause disease in humans. In the future, we hope to test more species.
We found evidence of how the response is caused, but there may be other ways that we have not yet found.
In most cases, we saw increased resistance. But in some cases the response was to cause a greater sensitivity to an antibiotic or no change at all. However, we cannot assume that increasing sensitivity will result in a reduction in antibiotic resistant strains.
Have these results been replicated?
Yes, we conducted our own blind replication by sending the bacteria and chemicals to a researcher at a different university without telling her what they were. She used our protocols and confirmed our findings and then became part of the author team.
Item 3
Herbicides can cause bacterial antibiotic resistance
Tuesday, 24 March 2015, 5:10 pm
Press Release: University of Canterbury
Herbicides can cause bacteria to become resistant to antibiotics
March 24, 2015
Research lead by a team from the University of Canterbury has found that commonly used herbicides can cause bacteria to become resistant to antibiotics.
Herbicides are used to kill plants. They can be tested for killing bacteria, too, as part of the process of reviewing their approval for use. However, they have never been tested for other effects on bacteria, University of Canterbury’s Professor Jack Heinemann says.
This is the first study of its kind in the world. While other substances such as aspirin have been shown to change bacteria’s tolerance to antibiotics herbicides have never been tested. The team at the University of Canterbury investigated what happens to species of disease-causing bacteria when they are exposed to common herbicides such as Roundup, Kamba and 2,4-D.
“We found that exposure to some very common herbicides can cause bacteria to change their response to antibiotics. They often become antibiotic resistant, but we also saw increased susceptibility or no effect. In most cases, we saw increased resistance even to important clinical antibiotics,” Professor Heinemann says.
“We were so surprised by what we were seeing. We wanted to be sure it wasn’t an artefact of conditions in our laboratory or some kind of contamination. So we enlisted a fellow researcher at Massey who conducted the same experiments but without knowing what she was adding to the bacteria. She got the same results.”
The effects found are relevant wherever people or animals are exposed to herbicides at the range of concentrations achieved where they are applied. This may include, for example, farm animals and pollinators in rural areas and potentially children and pets in urban areas. The effects were detectable only at herbicide concentrations that were above currently allowed residue levels on food.
Antibiotic resistance is a serious and growing problem for human and animal health. New antibiotics are hard to find and can take decades to become available. Effects of chemicals such as herbicides could conflict with measures taken to slow the spread of antibiotic resistance.
The research team included researchers from Mexico, Lincoln University and Massey