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Herbicides linked to antibiotic resistance

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New Zealand researchers have found that the active ingredients in commonly-used weed killers like Round-up and Kamba can cause bacteria to become less susceptible to antibiotics. The study builds upon research published in 2015 that found three common herbicides caused E.coli and Salmonella to become less sensitive to antibiotics. The new research investigated which ingredients were responsible and found it was the active ingredients, not the extra additives, to blame. The researchers suggest regulators should consider these impacts when considering whether such products are safe to use.

Journal/conference: Microbiology

Organisation/s: University of Canterbury, Lincoln University, University of Massachusetts, USA

Funder: Funding was received from a variety of source none of whom played any role in the study, preparation of the article or decision to publish. This project received funding from the Brian Mason Trust (JAH) and donations to the UC Foundation (JAH) including from, inter alia, donors Third World Network (Malaysia) and the Sustainable Food Trust (UK).

Media Release

From: University of Canterbury

New research finds common herbicides cause antibiotic resistance

New University of Canterbury research confirms that the active ingredients of the commonly used herbicides, RoundUp, Kamba and 2,4-D (glyphosate, dicamba and 2,4-D, respectively), each alone cause antibiotic resistance at concentrations well below label application rates.

UC Molecular Biology and Genetics Professor Jack Heinemann, of the School of Biological Sciences, in UC’s College of Science, says the key finding of the research was that “bacteria respond to exposure to the herbicides by changing how susceptible they are to antibiotics used in human and animal medicine.”

The herbicides studied are three of the most widely used in the world, including New Zealand, Professor Heinemann says.

“They are among the most common manufactured chemical products to which people, pets and livestock in both rural and urban environments are exposed. These products are sold in the local hardware store and may be used without training, and there are no controls that prevent children and pets from being exposed in home gardens or parks. Despite their ubiquitous use, this University of Canterbury research is the first in the world to demonstrate that herbicides may be undermining the use of a fundamental medicine-antibiotics.”

The new paper led by University of Canterbury (UC) researchers also finds that inert ingredients (surfactants) that are commonly used in some herbicide formulations and processed foods also cause antibiotic resistance. The new study found an antibiotic resistance response was caused by both the tested surfactants, Tween80 and CMC. Both are also used as emulsifiers in foods like ice cream and in medicines, and both cause antibiotic resistance at concentrations allowed in food and food-grade products.

With expertise in genetic engineering, bacterial genetics and biosafety, Professor Heinemann has some recommendations: “The sub-lethal effects of industrially manufactured chemical products should be considered by regulators when deciding whether the products are safe for their intended use,” he says.

“More emphasis needs to be placed on antibiotic stewardship compared to new antibiotic discovery. Otherwise, new drugs will fail rapidly and be lost to humanity.”

The researchers first observed this antibiotic resistance in their paper published in the American Society of Microbiology’s journal mBio in 2015. This follow-up study was conducted in order to identify which ingredients in herbicides were responsible.

Antibiotic resistance is the cause of nearly a million additional deaths worldwide from infectious diseases, Professor Heinemann says.

“The United States, for example, estimates that more than two million people are sickened every year with antibiotic-resistant infections, with at least 23,000 dying as a result. By 2050, resistance is estimated to add 10 million annual deaths globally with a cumulative cost to the world economy of US$100 trillion. In other words, roughly twice the population of New Zealand will be lost annually to antibiotic resistance.”

Background

Herbicides are chemicals used to control weeds. Because they kill organisms, they are biocides. As their primary purpose is to kill plants, their effects on some non-target organisms are not as well studied.

Antibiotics are also biocides. Antibiotic resistance allows bacteria that previously could be controlled by antibiotics to continue to cause disease and remain infectious for longer, even in the presence of antibiotics. Resistance to at least one major clinical antibiotic is now found in all human pathogens, and some important pathogens can be resistant to all but one antibiotic, or even all antibiotics. Even in wealthy countries, antibiotic resistance is responsible for billions of dollars of increased health care costs, additional suffering and tens of thousands of deaths each year.

Many biocides have effects on either target or non-target organisms at concentrations that do not kill. These are called sub-lethal effects. When pesticides, including herbicides, are reviewed for their safety by regulators, the focus is on acute and sometimes chronic toxicity using mortality as an endpoint. Much less information is sought on potential sub-lethal effects, particularly for microbes.

“Where this information is sought, it is usually only for people or animals. We are unaware of any regulator ever considering the risk of sub-lethal effects on bacteria. That is what makes this new research so important.”

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Expert Reaction

These comments have been collated by the Science Media Centre to provide a variety of expert perspectives and reflect independent opinion on this issue. Feel free to use these quotes in your stories. Views expressed are the personal opinions of the experts named. They do not represent the views of the SMC or any other organisation unless specifically stated.

Dr Siouxsie Wiles, Microbiologist and Senior Lecturer at the University of Auckland.

This paper is very timely, as this week is World Antibiotic Awareness Week in which the World Health Organization, the Ministry of Health, the Royal Society Te Apārangi and others are raising awareness of the crisis of antibiotic resistance. Antibiotics are losing their ability to kill bacteria. This means that we face a future in which routine surgery and medical treatments such as chemotherapy will be life-threateningly risky, and common infections untreatable. This crisis is caused in part because bacteria are able to mutate to become resistant to antibiotics, and because the discovery of new antibiotics has ground to a halt over the last few decades.

This paper by Professor Jack Heinemann and his colleagues builds on their earlier work looking at the impact of pesticides on bacteria. Now they have shown that exposure of two common gut bacteria to commercial pesticide formulations and some of their active ingredients can change how much antibiotic is needed to kill the bacteria. The bacteria they have examined (Salmonella Typhimurium and Escherichia coli) are both able to infect humans and other animals, including farm animals.

Prof Heinemann’s findings show how complex biology and the microbial world are. Some of the ingredients made the bacteria more sensitive to some antibiotics, and others made them less sensitive to antibiotics. Fortunately, the type of resistance Prof Heinemann and his colleagues found is not the type that can transfer from one species of bacteria to another, but it is clearly still cause for concern.

For me, their most striking finding was that surfactants, which are inert ingredients commonly used in all sorts of products, also increased resistance of the bacteria to various antibiotics. This means that it’s likely that many of the products we routinely use in our environment, our homes and on our bodies, may be contributing to making some bacteria more difficult to treat with antibiotics. With the crisis we are facing, that’s a real worry.

Last updated: 17 Nov 2017 8:43am
Dr Heather Hendrickson, Senior Lecturer in Molecular Bioscience, Massey University

We are living in a microbial world and we have been affecting that world in ways that we have not fully grasped for much of the industrial era. Antibiotics are the set of drugs that we use to kill or disable bacterial pathogens that make us ill. Today, these important medicines are becoming less effective around the globe as bacteria become resistant to them due to our overuse.

This new paper by Kurenbach et al. is an attempt to understand the effects that some common Herbicides (weed killers) may be having on a set of the microbial multitudes in our soils. 

This paper follows up on the foundational work published in 2015 by the last author, Jack Heinemann, which found that herbicide exposure could change the ability of some bacteria to survive antibiotic exposure. Here, the mechanism of some of the antibiotic effectiveness appeared to be protein pumps called efflux pumps in the bacteria. Bacteria exposed to herbicide start to make these pumps and install them like bilge pumps that purge the herbicides rapidly. Antibiotics can then be jettisoned along with the herbicides when both are present.

 The results of these two studies are not simple but they are worthy of public note for the following reasons:

1)     Exposure to commonly-used herbicides have effects on microbes that can make the bacteria more likely to be killed by some antibiotics but also less likely to be killed by other antibiotics.

2)     The microbes used here was a pair of bacteria, Salmonella enterica and Escherichia coli, both of which can be human pathogens. These are both on the 2017 WHO bacteria for R&D into new antibiotics list as Priority 1 'critical concern'. 

3)     The antibiotics used in this study were clinically-relevant antibiotics that we are using in human medicine today like ciprofloxacin and kanamycin.

4)     The herbicides used in this study are available widely and there is little current regulation on their use.

5)     It was the active ingredients in the herbicides (not the extra, 'co-formulant' additives) that had the greatest effects on antibiotic effectiveness.

6)     The concentrations of herbicides and antibiotics used in this study were within ranges that might be experienced by bacteria we encounter daily.

The message from the paper is clear, we need to reconsider our use of herbicides in light of the effect that they are having on the microbial world.

Last updated: 17 Nov 2017 8:12am

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