Dear Friends and Colleagues

Herbicides Increase Antibiotic Resistance Evolution in Bacteria

Antibiotic resistance in our pathogens is caused by human activity and is a major challenge for public health. Recent research has found that some of the world’s most widely used herbicides like Roundup (glyphosate) and Kamba (dicamba) can increase the rate of antibiotic resistance development in bacteria by a factor of up to 100,000 times faster than occurs without the herbicide. Both herbicides are used on genetically modified crops engineered to tolerate them.

The scientists studied multiple bacteria including Salmonella andE. coli. E. coli accounts for 17.3 percent of clinical infections requiring hospitalization. The study found that even when herbicides make bacteria weaker or stronger, it still develops resistance, and when the chemicals in herbicides are combined with antibiotics, the rate of antibiotic resistance increases because the genetic makeup in the bacteria changes. A further finding is that bacteria may acquire antibiotic resistance in the environment at rates substantially faster than predicted from laboratory conditions.

The scientists concluded that neither reducing the use of antibiotics nor the discovery of new ones may be sufficient strategies to avoid the post-antibiotic era. This is because bacteria may be exposed to other non-antibiotic chemicals, like herbicides, that predispose them to evolve resistance to antibiotics more quickly. The study adds to a growing body of evidence that herbicides used on a mass industrial scale in agriculture, but not intended to be antibiotics, can have profound effects on bacteria, with potentially negative implications for medicine’s ability to treat infectious diseases caused by bacteria. Thus, antibiotic resistance may increase even if total antibiotic use is reduced, and new ones are invented, unless other environmental exposures are also controlled.

With best wishes,

Third World Network
131 Jalan Macalister
10400 Penang
Malaysia
Email: twn@twnetwork.org
Websites: http://www.twn.my/and http://www.biosafety-info.net/
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Item 1

AGRICHEMICALS AND ANTIBIOTICS IN COMBINATION INCREASE ANTIBIOTIC RESISTANCE EVOLUTION

Brigitta Kurenbach, Amy M.Hill, William Godsoe, Sophie van Hamelsveld and JackA.Heinemann
PeerJ
DOI10.7717/peerj.5801
12 Oct 2018
https://peerj.com/articles/5801/

Antibiotic resistance in our pathogens is medicine’s climate change: caused by human activity, and resulting in more extreme outcomes. Resistance emerges in microbial populations when antibiotics act on phenotypic variance within the population. This can arise from either genotypic diversity (resulting from a mutation or horizontal gene transfer), or from differences in gene expression due to environmental variation, referred to as adaptive resistance. Adaptive changes can increase fitness allowing bacteria to survive at higher concentrations of antibiotics. They can also decrease fitness, potentially leading to selection for antibiotic resistance at lower concentrations. There are opportunities for other environmental stressors to promote antibiotic resistance in ways that are hard to predict using conventional assays. Exploiting our previous observation that commonly used herbicides can increase or decrease the minimum inhibitory concentration (MIC) of different antibiotics, we provide the first comprehensive test of the hypothesis that the rate of antibiotic resistance evolution under specified conditions can increase, regardless of whether a herbicide increases or decreases the antibiotic MIC. Short term evolution experiments were used for various herbicide and antibiotic combinations. We found conditions where acquired resistance arises more frequently regardless of whether the exogenous non-antibiotic agent increased or decreased antibiotic effectiveness. This is attributed to the effect of the herbicide on either MIC or the minimum selective concentration (MSC) of a paired antibiotic. The MSC is the lowest concentration of antibiotic at which the fitness of individuals varies because of the antibiotic, and is lower than MIC. Our results suggest that additional environmental factors influencing competition between bacteria could enhance the ability of antibiotics to select antibiotic resistance. Our work demonstrates that bacteria may acquire antibiotic resistance in the environment at rates substantially faster than predicted from laboratory conditions.

Item 2

GLYPHOSATE AND DICAMBA HERBICIDES INCREASE ANTIBIOTIC RESISTANCE IN BACTERIA

12 Oct 2018
https://www.gmwatch.org/en/news/latest-news/18508

A new study has found that some of the world’s most widely used herbicides, Roundup (glyphosate) and Kamba (dicamba), increase the rate of antibiotic resistance development in bacteria by a factor of up to 100,000 times faster than occurs without the herbicide.

Both herbicides are used on GM crops engineered to tolerate them.

The new study adds to a growing body of evidence that herbicides used on a mass industrial scale, but not intended to be antibiotics, can have profound effects on bacteria, with potentially negative implications for medicine’s ability to treat infectious diseases caused by bacteria. University of Canterbury (New Zealand) Professor Jack Heinemann, one of the study’s authors, said, “The combination of chemicals to which bacteria are exposed in the modern environment should be addressed alongside antibiotic use if we are to preserve antibiotics in the long-term."

An important finding of the new study was that even in cases where the herbicides increase the toxicity of antibiotics they also significantly increased the rate of antibiotic resistance, which the authors say could be contributing to the greater use of antibiotics in both agriculture and medicine.

Previously these researchers found that exposures to the herbicide products Roundup, Kamba and 2,4-D or the active ingredients alone most often increased resistance, but sometimes increased the susceptibility of potential human pathogens such as Salmonella enterica and Escherichia coli, depending on the antibiotic.

Prof Heinemann said, “We are inclined to think that when a drug or other chemical makes antibiotics more potent, that should be a good thing. But it also makes the antibiotic more effective at promoting resistance when the antibiotic is at lower concentrations, as we more often find in the environment. Such combinations can be like trying to put out the raging fire of antibiotic resistance with gasoline.”

The authors concluded that neither reducing the use of antibiotics nor the discovery of new ones may be sufficient strategies to avoid the post-antibiotic era. This is because bacteria may be exposed to other non-antibiotic chemicals that predispose them to evolve resistance to antibiotics more quickly. Herbicides are examples of some of the most common non-antibiotic chemicals in frequent global use. Thus antibiotic resistance may increase even if total antibiotic use is reduced, and new ones are invented, unless other environmental exposures are also controlled.

The new paper, “Agrichemicals and antibiotics in combination increase antibiotic resistance evolution” is published online in the peer-reviewed journal PeerJ on October 12 and can be downloaded without charge from here: https://peerj.com/articles/5801/
Notes

1. Kurenbach, B., Marjoshi, D., Amabile-Cuevas, C.F., Ferguson, G.C., Godsoe, W., Gibson, P. and Heinemann, J.A. 2015. 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. Mbio 6, e00009-00015. Kurenbach, B., Gibson, P.S., Hill, A.M., Bitzer, A.S., Silby, M.W., Godsoe, W. and Heinemann, J.A. 2017. Herbicide ingredients change Salmonella enterica sv. Typhimurium and Escherichia coli antibiotic responses. Microbiology 163, 1791-1801.

Item 3

COMMONLY USED HERBICIDES ARE MAKING BACTERIA MORE RESISTANT TO ANTIBIOTICS, RESEARCHERS SAY

By Abbey Interrante
Newsweek
13 Oct 2018
https://www.newsweek.com/antibiotic-resistance-occurs-100000-faster-herbicides-1168034

Commonly used herbicides can make bacteria develop antibiotic resistance significantly faster.

Researchers at New Zealand’s University of Canterbury and Lincoln University looked into how herbicides that are used on a mass industrial scale affect bacteria in the latest research pointing to a harmful connection. Published in PeerJon Friday, the study revealed the speed of antibiotic resistance and how easily it can happen.

“Herbicides are among the most widely used and dispersed manufactured products on Earth. Some form of exposure for people, pets and livestock can be routinely expected,” Jack Heinemann, professor at the University of Canterbury and author on the paper, told Newsweek. “Meanwhile, antibiotics are used at high rates particularly on people, pets and livestock. Therefore, the combination of exposures for bacteria that live on us is all but guaranteed.”

Heinemann and his team have researched this before and published papers in 2015 and 2017 showing the link between antibiotic resistance and herbicides. This paper’s new findings are that even when herbicides make bacteria weaker or stronger, it still develops resistance, and when the chemicals in herbicides are combined with antibiotics, the rate of antibiotic resistance increase because the genetic makeup in the bacteria changes.

“That is why we call the herbicides gasoline for a fire,” Heinemann explained. Antibiotics don’t stay where we use them—they spread through feces, urine, and drains. As the antibiotics travel away, they encounter bacteria that could become resistant to them. The use of herbicides is only growing the areas that the antibiotics might meet these potentially-resistant bacteria.

“However, we were surprised at how powerful these formulations were for boosting resistance in populations of bacteria, and at how low the concentration of herbicide could be for this to happen. The concentrations we tested were well below application levels,” Heinemann said.

The researchers studied multiple bacteria including Salmonella andE. coli. E. coli accounts for 17.3 percent of clinical infections requiring hospitalization, according to the Broad Institute. In some cases they tested, resistance evolved 100,000 faster when exposed to herbicides like Roundup, made with glyphosate or Kamba, made with dicamba. The scientists don’t know yet if these reactions are directly affecting our ability to treat illnesses right now, but they think it’s likely. 

“Even small changes in resistance can complicate, even compromise, antibiotic therapy. In many cases, therapy could fail and the reasons not be diagnosed. Effects such as we observe might explain some of those cases,” Heinemann said. However, it’s still possible to start working to avoid the effects.

“The first step is to acknowledge that this is an issue. Once that is done, we and others, including manufacturers of chemical products that we are routinely exposed to, can study the sub-lethal effects on bacteria,” Heinemann said. “Where effects are found, proper monitoring can be done to limit effects. We think that it is time for safety regulators to begin asking for such studies from manufactures at the time that they submit their products for regulatory approval.”