Analysis of historic soil archives dating back to 1923 has revealed a clear parallel between the appearance of antibiotic resistance in medicine and similar antibiotic-resistant genes detected over time in agricultural soils treated with animal manure.

Collected in Denmark, where antibiotics were banned in agriculture from the 1990s for non-therapeutic use, the soil archives provide an ‘antibiotic resistance timeline’ that reflects resistant genes found in the environment and the evolution of the same types of antibiotic resistance in medicine.

Led by Newcastle University, UK, study also showed that the repeated use of animal manure and antibiotic substitutes can increase the capacity of soil bacteria to mobilise, or ready themselves, and acquire resistance genes to new antibiotics.

The authors of the study, published in the journal Scientific Reports, said the data highlights the importance of reducing antibiotic use across all sectors if global antibiotic resistance is to be reduced.

Dr Charles Knapp, a Senior Lecturer in Strathclyde’s Department of Civil & Environmental Engineering, was a partner in the research. He said: “Antibiotic resistance is a major global concern which threatens to decrease the effectiveness of antibiotics to treat infections and illness. Resistant infections also lead to treatment costs and lost productivity.

“The origins of antibiotic resistance remain unclear; hospitals and agriculture are often blamed but there may be less apparent factors. Using archived soils and DNA analysis, we were able to get a picture of what the bacteria communities were like in the environment over the past 90 years.

“From this information, we found that antimicrobial resistance has been increasing in nature since the industrial production of antibiotics and that clinical infections occur about the same time that resistance genes become apparent in nature — this does not suggest that one causes the other but their appearance makes almost a universal impact. We also concluded that policy and appropriate preventative measures could become effective to reduce the threat of antibiotic resistance—if appropriately followed.

“At Strathclyde, we routinely develop and use genetic assays for the detection of antibiotic and antimicrobial resistant bacteria and their genes. We are looking to understand the origins of resistance traits and to minimise strategically their impact on society and the economy.”

Antibiotics have been used in medicine since the 1930s, saving millions of lives. Two decades later they were introduced into agricultural practices and Denmark was among the leaders in employing antibiotics to increase agricultural productivity and animal production.

However, a growing awareness of the antibiotic resistance crisis and continued debate over who and which activities are most responsible led to the EU calling for the use of antibiotics in non-therapeutic settings to be phased out and Denmark led the way.

The Askov Long-Term Experiment station in Denmark was originally set up in 1894 to study the role of animal manure versus inorganic fertilisers on soil fertility.

Analysing the samples, the team – also involving researchers from Aarhus University – was able to measure the relative abundance of specific β-lactam antibiotic resistant genes, which can confer resistance to a class of antibiotics that are of considerable medical importance.

Prior to 1960, the team found low levels of the genes in both the manured soil and that treated with inorganic fertiliser. However, by the mid 1970’s, levels of selected β-lactam genes started to increase in the manured soils, with levels peaking in the mid 1980’s. No increase or change was detected in the soil treated with inorganic fertiliser.

Following the ban on non-therapeutic antibiotic use in Danish agriculture, farmers substituted metals for antibiotics, such as copper, and levels of the key β-lactam genes in the manured soils declined rapidly, reaching pre-industrialisation levels by 2010.

However, at the same time the team measured a 10-fold rise in Class 1 Integrons. These are gene carrier and exchange molecules – transporters which allow bacteria to readily share genes, including resistance genes.

These findings suggest the application of manure and antibiotic substitutes, such as copper, may be ‘priming’ the soils, readying them for increased resistance transmission in the future.



University of Strathclyde

Newcastle University

Appearance of β-lactam resistance genes in agricultural soils and clinical isolates over the 20th century. David W Graham, Charles W Knapp, Bent T Christensen, Seanin McCluskey and Jan Dolfing. Scientific Reports