Scientist challenges EPA over antibiotic resistance

The Environmental Protection Agency is being challenged to look beyond the overuse of human antibiotics to explain an alarming increase in antibiotic resistance.

New research links the active ingredients in common weedkillers – and inert ingredients called surfactants, which are also used in processed foods – to an increase in antibiotic-resistant bacteria.

The study, published in the journal Microbiology, goes beyond 2015 research which tested commercial formulations of well-known herbicides, such as Roundup and Kamba.

One of the Microbiology paper’s authors, University of Canterbury’s Jack Heinemann, agrees antibiotic use causes resistance. But his laboratory research shows there might be other factors, which are combining to cause a crisis in antibiotic resistance.

“Unless we identify all of the different ways in which our activities are causing resistance, then we can’t hope to preserve the use of antibiotics,” he tells Newsroom.

Further research is needed, Heinemann says, to test the effect on humans or animals.

Antibiotic resistance allows disease-causing bacteria previously controlled by antibiotics to persist and reproduce, making them infectious for longer.

Linking weedkillers and antibiotic resistance is a twist on a worldwide threat that is so severe, England’s chief medical officer, Professor Dame Sally Davies, is warning it could be the end of modern medicine and cause a “post-antibiotic apocalypse”.

There are fears that without the use of antibiotics, cuts and scratches might become life-threatening.

It’s estimated 700,000 people around the world die each year because of drug-resistant infections. That might rise to 10 million people a year by 2050 if nothing is done. By then, the cost to the global economy could be as high as $US100 trillion, according to one estimate.

“It needs a lot more testing in the real field to see how important the effect is in reality.”

Heinemann says more needs to be known about the effect on microbes by commercially-made chemicals, which are used ubiquitously without regulation by governments and people in cities and on farms.

He zeroes in on “sub-lethal” effects which, he says, could lead to changes in bacteria’s susceptibility to antibiotics.

Environmental Protection Authority chief scientist Jacqueline Rowarth tells Newsroom that, at the moment, it’s thought antibiotic resistance is caused by the overuse of human antibiotics, “not by things like this”.

She says the results of the Microbiology research’s lab tests were inconsistent and “small”.

“It needs a lot more testing in the real field to see how important the effect is in reality.

“We always look at new research for implications for our current usage or regulations. And so we will keep watching this and all the reports around it to see if there are any major points of concern.”

Heinemann responds: “The EPA should be saying we really want to know whether or not we could handle herbicides differently and avoid this potential outcome.”

Dr Siouxsie Wiles, a microbiologist at the University of Auckland who specialises in infectious diseases, says bacteria can mutate by chance and those mutations can make them more or less susceptible to antibiotics. Resistant strains get an advantage and thrive wherever antibiotics are present.

Depending on the kind of resistance, bacteria can transfer that to other unrelated bacteria.

“This can happen wherever bacteria meets – so it can be happening in our gut, it can happen in the guts of animals, it can happen in the soil, all of these types of places.”

Antibiotic-resistance through so-called efflux pumps, highlighted by Heinemann's research, is different, Wiles says.

“If you have a bacteria that’s had this exposure, it’s producing these pumps a bit more and is then less susceptible to the antibiotics. That could potentially be a problem if a person’s infected with it.”

Antibiotics pumped out

Heinemann’s research involved testing the antibiotic resistance of E.coli and Salmonella enterica bacteria after treatment by active ingredients and surfactants.

The Microbiology journal paper explains the work of efflux pumps, which work the same way as bilge pumps on boats. Toxins flow into a cell, across its membrane, and the efflux pumps protect them by pumping them back out. Herbicides and antibiotics, which are both biocides, are toxins.

Heinemann: “That’s the interesting thing about these efflux pumps – if they’re turned on by something that’s not very toxic, they vaccinate the bacterium against things that are toxic.

“And they will pump out a variety of different antibiotics all at once and that’s why we call it a multiple-drug resistance.

“What we saw was, if they became resistant to one antibiotic they generally became resistant to several all at once.”

For example, glyphosate, the active ingredient in Roundup, makes salmonella much more resistant to antibiotic drugs called aminoglycosides. And it makes them much more resistant to fluroquinolone drugs, such as ciprofloxacin. Ciprofloxacin is an important anti-E.coli antibiotic, used to combat bladder and urinary tract infections.

But if you expose bacteria to dicamba, the active ingredient in Kamba, they become more susceptible to aminoglycoside antibiotics. That means it takes less aminoglycoside in the petri dish to kill them.

Surely that’s a good thing? Not so fast, Heinemann says. He says greater susceptibility increases the “selective power” of antibiotics, which can also result in bacteria evolving resistance.

The herbicide causes the bacteria to compete with each other at lower concentrations of antibiotic, he says, with the more resistant ones taking over the population.

“In both scenarios, at different antibiotic concentrations, the combination of the herbicide and the antibiotic is favouring the evolution of resistance.”

Most people won’t ingest enough herbicide at the concentrations necessary for resistance, he says, because of legally mandated maximum residue limits.

But his research found emulsifiers – like polysorbate 80 and carboxymethylcellulose – at concentrations in food that do cause resistance.

“There, an ingestion pathway is plausible for inducing this in our gut bacteria.”

While there are maximum concentrations set for emulsifiers in food, there are no such limits in herbicides.

Newsroom asked Monsanto for comment, to see if its research matches up with the Microbiology paper. This morning, spokesman Cole Waggoner said via email that the company was reviewing the study. He said the same researchers published a very similar study in 2015 and the conclusions were rejected by the European Food Safety Authority, the European Chemicals Agency and New Zealand's EPA.

"Glyphosate safety is supported by one of the most extensive human health, crop residue and environmental databases ever compiled on a pesticide product. Like all pesticides, regulatory authorities around the world routinely review the latest safety data on glyphosate. In evaluations spanning four decades, the overwhelming conclusion of experts worldwide has been that glyphosate can be used safely."

Global health threat

New Zealand’s Ministry of Health says antimicrobial resistance – including bacteria that have developed resistance to multiple classes of bacteria – is a global health threat that is getting worse. Several studies state infections caused by multi-drug-resistant micro-organisms are increasing across the country.

Researchers across the world are now in a race to develop antibiotics that can kill multi-drug resistant superbugs. They include Victoria University of Wellington researchers who, in June, were awarded a $1.2 million grant from the Health Research to find new antibiotics from previously untapped sources.

Heinemann says antibiotic resistance returns quickly when an antibiotic returns to a country or marketplace – at a pace much faster than the first time the drug was used.

“This tells us strongly that it’s more than just the antibiotic that we have to deal with. What those other things are, I don’t know. But unless we’re actively researching these things we won’t know.”

New Zealand needs a good, hard look at regulations governing weed-killing chemicals, he says. Risk assessments should be done to ensure they’re being used appropriately.

After such an assessment, Heinemann says it might be deemed appropriate to spray herbicides on paddocks.

“But it may not be appropriate to sell it in the local hardware store, where in a concentrated urban setting, where children and pets might walk through treated areas that are not indicated as being treated, there it may not be a risk that we can any longer mitigate.”

He adds the very scientific qualifier: “It may or may not be.”

Options can only be considered when regulators are aware of the risk, Heinemann says.

“We do have to live, probably, in a less chemically intensive world because we haven’t appreciated just all the ways in which our ecosystems, including our bodies, are being affected by this choice to live through chemistry.”

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