Global study shows widespread latent antimicrobial resistance in wastewater

Global study shows widespread latent antimicrobial resistance in wastewater

A team of researchers has found that latent antimicrobial resistance is more widespread worldwide than known resistance. They call for more comprehensive monitoring of resistance in wastewater, as the problematic genes of the future may be hiding in the widespread reservoir of latent resistance genes. The research was published in Nature Communications.

A group of researchers analyzed 1,240 wastewater samples from 351 cities in 111 different countries and found that bacterial latent antimicrobial resistance is widespread on all continents around the world. The research was coordinated by the DTU National Food Institute in Denmark. The antimicrobial resistance genes examined do not currently pose a major risk, but some of them are likely to pose a major risk in the future, according to the researchers, who based on the study recommend increased monitoring of antimicrobial resistance in wastewater. The research was published in the renowned journal Nature Communications (insert link:

“Research shows that we have a latent reservoir of antimicrobial resistance that is much more widespread worldwide than we expected,” says researcher Hannah-Marie Martiny, who is the first author of the study together with Associate Professor Patrick Munk from the DTU National Food Institute.

The researchers compared the geographic distribution of latent and already active antibiotic resistance genes (hereafter referred to as acquired) and found a much larger geographic distribution of latent resistance genes than acquired ones.

In order to contain future antimicrobial resistance, we believe that routine monitoring of antimicrobial resistance in wastewater should include latent resistance genes in addition to already acquired resistance genes in order to address tomorrow's problems."

Patrick Munk, Associate Professor, DTU National Food Institute

Consistent with previous research, the study shows that acquired resistance genes are present in greater abundance in sub-Saharan Africa, South Asia and the Middle East and North Africa (MENA) regions than in other parts of the world.

Hope of being able to contain a pandemic

It's natural for bacteria to have genes that can make them resistant to antibiotics. Such genes are found everywhere, for example in soil, water and in humans. However, our use of antibiotics and other environmental pressures (see section “Environmental Pressures Determine Antimicrobial Resistance” below) have driven the spread of resistance to such an extent that the World Health Organization (WHO) has designated antimicrobial resistance (AMR) as a pandemic (insert link:

When researchers around the world study the scale and spread of the problem, they typically focus on resistance genes that are already capable of switching between bacterial hosts. Acquired antibiotic resistance genes pose a real challenge because they make it difficult or impossible to treat humans and animals with antibiotics.

Expanded surveillance would provide hope that researchers can determine where and how antimicrobial resistance arises and spreads, and that they can map the ecology of genes.

"By tracking both acquired and latent antimicrobial resistance genes, we can gain a comprehensive overview of how they evolve, change hosts and spread in our environment, thereby taking more targeted action against antimicrobial resistance (AMR). Wastewater is a practical and ethical way to monitor AMR as it accumulates waste from humans, animals and the immediate environment," says Hannah-Marie Martiny

The study also shows that there are more latent resistance genes distributed worldwide than acquired resistance genes. Only in sub-Saharan Africa are there the same number.

"In general, I don't think we need to worry too much about most latent antimicrobial resistance genes, but I think that some of them will cause problems at some point, and we would like to know which ones. Because with this knowledge we can perhaps predict which bacteria can be stopped by which drugs in the future," says Hannah-Marie Martiny; A view that Patrick Munk also shares.

"As new antibiotics are developed - a process that takes many years - bacteria may have already invented new 'scissors' that can destroy them. If we can study both types of genes over time, we may be able to figure out which of the latent genes become problematic resistance genes, how they arise and how they spread across the region and bacteria, and in this way reduce the burden of antimicrobial resistance," says Patrick Munk.

Latent antibiotic resistance mapped using functional metagenomics

There are several ways to test whether genes confer resistance to antibiotics, both through AI-based predictions and laboratory experiments. However, computer predictions involve a certain amount of uncertainty, which can also distort the interpretation of the results.

Latent resistance genes are identified by extracting DNA from a sample and then testing random DNA fragments to determine whether they can confer antimicrobial resistance. The method is called functional metagenomics and involves inserting DNA fragments into a harmless bacterium. The surviving bacteria must have received a piece of DNA that provides resistance. This does not necessarily mean that the DNA fragment can move naturally between bacteria in the environment.

The difference between latent resistance genes and acquired resistance genes is precisely that acquired resistance genes are known to be able to jump to new bacterial hosts, while latent resistance genes can jump to new bacterial hosts in the laboratory. However, researchers do not yet know whether they will eventually be able to do this in the environment.

"Our concern is that some latent resistance genes become acquired resistance genes and are thus able to jump to different bacterial hosts in the environment. Especially because research also shows that they are present in large numbers in so many places around the world. That's why we would like to include them in surveillance," says Patrick Munk.

Researchers do not yet know to what extent latent resistance genes develop into problematic acquired resistance genes. Comprehensive monitoring of both latent and acquired resistance genes will help answer this question.

May prevent the treatment of infectious diseases

The classic way in which society becomes aware of acquired resistance genes is through infectious diseases that cannot be treated with antibiotics due to resistance. At the DTU National Food Institute there is a large collection of resistance genes (insert link:) that is used by doctors and researchers worldwide when they need to determine whether a bacterium is antimicrobial resistant. In the present study, the presence of all different resistance genes in the wastewater samples was quantified to determine their geographical and ecological distribution.

Environmental pollution determines antimicrobial resistance

The environment acts as a referee in a constant race of elimination when it comes to resistant bacteria. When antibiotics are present, the susceptible bacteria die first. The few bacteria that initially carry a resistance gene survive and multiply. The following factors in the environment, for example, influence which bacteria die and which survive:

• Rückstände von Antibiotika in der Umwelt (aus Krankenhäusern, der Landwirtschaft, Abwasser) hemmen oder töten anfällige Bakterien und verschaffen resistenten Bakterien einen Vorteil, da sie sich leichter verbreiten können.
• Desinfektionsmittel und Biozide können bei wiederholter oder längerer Einwirkung Bakterien selektieren, die diese Mittel vertragen. Diese Bakterien tragen oft auch Gene, die eine antimikrobielle Resistenz verleihen.

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