Antibiotics mix up bacterial competition – to the detriment of humans

A large share of antibiotic courses end up in the sewage, progressing to the sea through water treatment plants. Drugs brewing up in sludge and water further the march of dangerous bacteria.

A water treatment plant as an incubator of super bacteria – a chilling thought. According to Docent Marko Virta, a microbiologist, it’s not that far-fetched an idea after all.

When microbes originating in human and animal guts cross paths with each other and environmental bacteria, they start concrete and efficient interaction: bacteria swap genes, regardless of the boundaries between species. Both pathogens and harmless microbes are accepted into this “recycling club”.

Bacteria resistant to antibiotics are often born when a gene underlying antimicrobial resistance is transmitted between two bacterial species. Transmission is more likely between closely related species, but also possible between very distant relatives.

A serious global threat

“Usually, the origin of resistance can be tracked to the microbe that naturally produces the antibiotic in question. Antibiotics, or at least drug models, originate most often in bacteria,” reminds Virta, who works at the Helsinki Institute of Sustainability Science of the University of Helsinki.

Virta stresses that the problem caused by antibiotics that end up in the toilet in human urine is not based on their toxicity after passing through water treatment plants to the sea. The danger lies in the fact that an environment laced with antibiotics will narrow down the habitat available to “nice” bacteria, or bacteria sensitive to antibiotics. By handling drugs recklessly, we are playing into the hands of resistant bacteria.

Resistance genes that are transmitted between species eventually end up inside problematic pathogens, and people start to die.

A clean Helsinki

StARE, a research project under which Marko Virta is working, has compared the bacteria-filtering capacity of water treatment plants in seven EU states. As a rule, even bacteria are caught in the filters, provided that the original mission of the plant, namely the removal of nutrients, is carried out well.

In Europe’s largest treatment plant Viikinmäki, located in Helsinki, the amount of bacteria in water can be reduced to as little as one thousandth of the original, reducing the number of resistant bacteria in the same proportion. Even at the worst times, bacterial numbers shrink to one percentage of the original.

Measuring treatment efficiency is not as straightforward as you might think: it’s not as simple as pouring water processed at the plant into a petri dish, after which you just wait for any potential bugs to multiply.

“Bacteria are everywhere, and in favourable conditions their growth is very efficient. Therefore, it’s somewhat surprising that only a small portion of bacteria can be cultured with the current techniques,” says Virta.

Environmental bacteria are indeed tracked by looking for their molecules, usually genes. “This suits well for research on antimicrobial resistance, since that trait is based specifically on genes.”

Virta and his colleagues have searched for gene sequences from bacteria resistant to antibiotics also from the seafloor in the areas where the outlet pipes of treatment plants are located. “The situation is excellent near Helsinki. There’s practically nothing there.”

StARE: controlling environmental hazards

The StARE project (@STARE_WATER) is investigating the journey of antibiotics and bacteria resistant to antibiotics to treatment plants and further. The project’s acronym comes from Stopping Antibiotic Resistance Evolution.

The researchers aim to find out what kind of a role urban European water treatment plants have in the rise in prevalence of antimicrobial resistance. For now, resistance has mainly been investigated in clean conditions, even though sewage is a favourable environment for bacterial evolution.

StARE is drafting guidelines for monitoring resistance at treatment plants and developing technical solutions in preventing its spread. Research findings are also utilised in developing the EU’s Water Framework Directive.

The research consortium is composed of experts in genetics, microbiology, public health, chemistry and civil engineering from Spain, Ireland, Cyprus, Norway, Portugal, Germany and Finland. From Finland, the University of Helsinki is participating under the direction of Marko Virta. The Academy of Finland has provided support for the work through its Sustainable Governance of Aquatic Resources programme.

Poo in the compost heap

At Viikinmäki, the plant accrues 170 tons of treatment sludge every day. The phosphorus contained in the sludge in particular makes it a valuable fertiliser, but there is heated debate on its use and safety. “In Finland, opportunities for using sludge are good, since metal residues are at a low level and water treatment plants aren’t doubling as incubators for resistant bacteria,” assesses Virta.

To the researcher’s grief, companies are loath to take up the challenge for fear of tarnishing their reputation. Can consumers stomach the idea about faeces? What if a potent microbe still manages to get through?

The sludge from the largest plant in Europe does not end up in a grain field, but the decomposed and dried material is composted in a neighbouring municipality. The resulting soil is used in landscaping.

Advice for physicians

What about the antibiotics that first go through a human body or end up directly in the sewer? For them, even a treatment plant with first-class operations is not the right solution. Filtering half of the drugs is already a good result.

Due to the poor absorbability of antimicrobial drugs, the culture of drug use is an essential part of the risk. The amount of drugs flowing through the human body is greater than that absorbed by it.

According to Virta, medical culture in the Nordic countries is no-nonsense: antibiotics are only used when necessary, with the possible exception of pets. He praises the manner in which drug sales have been organised in Finland: a prescription is required for purchasing many drugs, and the physicians writing the prescriptions have no part in drug sales.

“In many countries, doctors sell drugs, often gaining a large share of their income through drug sales. In such situations, the justification for all prescriptions may not exactly be watertight.”

Antibiotics washed into the environment go through various stages depending on the active ingredient or even the brand of the drug. A reimbursement system favouring the cheapest products is problematic, since products known as generic drugs are often more harmful to the environment.

“In our neighbouring country Sweden, physicians are instructed in the environmental effects of drugs. They are guided to prescribe antibiotics that break up easily after exiting the body. Variation and choices abound.” In Sweden, consideration is currently given to whether to put an end to favouring the most inexpensive option.

Price is everything

Croatia and France are Europe’s largest producers of antibiotics. All in all, the pharmaceutical industry is a dying sector in the west, with production outsourced to Asia in particular. Africa is most likely next in line. On these continents, environmental norms are often lax and control is inadequate.

“At a scientific conference, I heard of a case where a modern water treatment plant built for a Chinese drug manufacturer is not used at all, since it would raise production costs and prices. Thus, the company would no longer make it in the price war. In India, some pharmaceutical manufacturing plants don’t have a treatment plant to begin with.”

Even Europe didn’t pass the StARE inspection with flying colours. Measurements conducted on weekdays at a Croatian drug plant were exemplary, but outside official control hours during weekends, residue was detected in the samples.

Resistant strains boosted by pollutants

Outsourcing and indifference will backfire, since risks related to antibiotics are not restricted even by continental boundaries. Marko Virta refers to a report ordered by the British government forecasting the status of antimicrobial medication in 2050.

“Unless problems are dealt with and if bacterial resistance keeps on growing, the number of annual casualties may rise from the current 700,000 to no fewer than 10 million.”

The situation is complicated by a minefield found in genetic research that has not received much attention. Namely, resistant bacteria are given the edge through other pollution as well, in addition to the overuse of antibiotics.

The same genetic sequence that safeguards bacteria against antibiotics also protects them from the effects of disinfectants, biocides, metals and other toxins, Virta explains. For instance, plasmid R100, one of the most thoroughly investigated DNA molecules, provides protection against four different antibiotics, mercury and biocides.

When we are spoiling the environment with, say, silver particles, copper and antibacterial detergents, we are once again depriving harmless bacteria of habitat while boosting resistant strains. In addition to treatment plants, toxins end up in ditches, rivers, lakes and seas used as sewers around the world.

What goes on at a treatment plant?

Cleaning nutrients from sewage is the primary duty of water treatment plants. In Europe’s largest treatment plant, located in Helsinki, Finland, the process is comprised of mechanical, biological and chemical treatment.
Good filtering also removes most of the bacteria in the water.

However, the filtration of pharmaceutical substances is relatively poor. In addition to drugs, many other toxins from heavy metals to fire-retardant chemicals also push through the filters.

Switzerland is the European model for water treatment, safely able to drain treated water into its lakes. Finnish water treatment plans also work well. In southern Europe, the situation regarding pharmaceutical substances is more challenging, partly due to the local medication culture.

Functional medicine is a wonder

“The more you know, the more you marvel at the existence of functioning antibiotics in the modern world,” muses Virta. “Everything used to fight bacteria turns into an adversary through the same mechanism.” According to Virta, alcohol is actually the only safe disinfectant. Alcohol is tolerated by all bacteria to more or less the same degree.

What’s more, laboratory experiments indicate that antibiotics activate those mobile genetic elements in which the resistance trait often resides. Antibiotics also increase bacterial mutations, which play a role in generating resistance. The triumph of resistance seems inevitable.

“There are solutions, but they require sufficient will,” Virta assures. Health care professionals’ awareness can be increased; the use of generic drugs, as well as antibiotic courses for production animals and pets, can be reduced, vaccines can be developed and disease diagnostics can be improved. Appropriate toilets and plumbing are also important.

Researchers are in a key position to come up with detailed plans. In Finland, recent discussion has revolved around shortening antibiotic courses, which has garnered both support and opposition from experts. The debate is still ongoing. “We need to learn much more about microbial evolution and living habits,” says Marko Virta.

Veterinary medicine and the African situation to be scrutinised

University Lecturer, Docent Marko Virta is working at the Helsinki Institute of Sustainability Science and the Department of Microbiology of the University of Helsinki. In May, the Academy of Finland awarded Virta’s research group funding for four years for its project Antibiotic resistance in animal production.

In addition, Virta is a partner in a research project Occurrence, sources and prevention of antimicrobial resistance in West Africa – following the flow of AMR genes between humans, animals and environment led by Anu Kantele, a professor of infectious diseases. The project is among a number of development studies projects jointly funded by the Academy of Finland and the Ministry for Foreign Affairs of Finland.

What’s antimicrobial resistance?

Antibiotics are molecules naturally produced by microbes, or at the very least the recipes for making drugs have been borrowed from microbes. From microbial perspective, resistance is nothing special: the bacteria producing these molecules must tolerate their own product.

The range of pathogens resistant to antibiotics grows when the gene underlying resistance is transmitted from one species of bacteria to another. The same genetic sequence that makes bacteria tolerate antibiotics also protects them from many other toxins, such as disinfectants, biocides and mercury.

Resistant bacteria pose a serious risk in many Asian and African countries. Plumbing and water treatment are often of a poor quality, and drug use is prevalent due to chronic diseases, inadequate health care and a lax drug culture.