A new study has found that exposure to the herbicides used on GM crops changes how susceptible disease-causing bacteria are to antibiotics. In many cases the bacteria became more antibiotic-resistant, though in other cases they became less so. The study was carried out by Prof Jack Heinemann, Dr Brigitta Kurenbach, and other scientists from New Zealand and Mexico. Below Prof Heinemann and Dr Kurenbach respond to questions from GMWatch.
GMW: What did you find?
When we exposed either of two different species of bacteria to common
herbicides that we purchased at a local store, we found that the
bacteria changed their response to antibiotics. They often became
antibiotic resistant, but we also occasionally saw increased
susceptibility or no effect.
GMW: Which herbicides and antibiotics are you talking about?
We tested commercial formulations of herbicides based on the active
ingredients dicamba, 2,4-D and glyphosate. The antibiotics were
representative of five major groups: β-lactams (ampicillin),
chloramphenicol, tetracycline, fluroquinolones (ciprofloxacin) and
GMW: Why does your study matter?
Every day you see in the news that there are concerns about the ever
increasing frequency of antibiotic resistance in bacteria that can cause
disease in people and our animals. Anything that contributes to this
problem should be considered because new antibiotics are rare.
The effects found may be relevant if people or animals are exposed to
herbicides at the higher ranges of concentration, those that occur when
it is applied rather than what is normally found on food. Those kinds of
exposures may be experienced by, for example, farm animals and
pollinators in rural areas and potentially children and pets in urban
Heinemann: And we can’t predict either the direction or
size of the observed effects based on bacterial species, antibiotic or
herbicide used. Thus, different potential disease-causing bacteria may
react differently to the same herbicide or to the same antibiotic.
GMW: Is this the first study to show this?
We’ve looked hard to find other studies like this, but haven’t found
any. Other studies have reported on other substances that also change
bacteria's tolerance to antibiotics (e.g. aspirin), but herbicides
GMW: What are the limitations of your study?
While we tested examples from most major groups of antibiotics, there
are more individual antibiotics than we could test. And our tests are in
the laboratory. We hope to get funding to test environmental samples or
bacteria from animals.
Kurenbach: We only tested two species of
bacteria. They were laboratory strains of disease-causing species. We’d
like to test the response of more species of bacteria.
genetic and biochemical evidence of how the bacteria become resistant
or sensitive. But there may be more ways than we have so far described.
GMW: Have these results been replicated?
As part of this study we engaged another scientist at another
university in a blinded replication. We sent her the bacteria and
chemicals through an intermediary who kept their identities a secret.
Using our protocols, she was able to confirm our findings. She also
later joined the author team.
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
Brigitta Kurenbach, Delphine Marjoshi, Carlos F.
Amábile-Cuevas, Gayle C. Ferguson, William Godsoe, Paddy Gibson, Jack A.
mBio 6(2):e00009-15. doi:10.1128/mBio.00009-15.
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 -galactosidase assays
with soxSlacZ fusion strains of E. coli. Dicamba was a moderate inducer
of the sox regulon. Growth assays with Phe-Arg -naphtylamide (PA 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.