Sublethal Antibiotics Boost Resistance Gene Spread 45x

A new study has found that exposure to sublethal levels of antibiotics, amounts too low to kill bacteria, can increase the spread of antibiotic resistance genes of Escherichia coli (E. coli) found in the environment by up to 45 times.

The study led by researchers from the University of Nottingham and Ineos Oxford Institute for antimicrobial research (IOI) analysed 39 E. coli strains from a UK dairy farm that were resistant to a group of widely used human critical antibiotics called cephalosporins.

Their findings published in Frontiers journal, showed that all 39 cephalosporin resistant E. coli strains carried the same resistance gene- blaCTX-M-15, which protects bacteria from penicillin and cephalosporin antibiotics

Genetic testing showed the bacteria were almost identical, suggesting a single strain had spread across the farm. Researchers also found that the resistance gene wasn't fixed in place- it could jump from the bacterial chromosome onto separate small circular double-stranded DNA molecules called plasmids, which can move between bacteria.

When these bacteria were exposed to low levels of antibiotics, the gene transfer rate shot up dramatically:

  1. Exposure to ceftazidime (an antibiotic used to treat serious bacterial infections) increased transfer by up to 45 times.
  2. Ampicillin and cloxacillin (penicillin-class antibiotics, often prescribed to patients as combination therapy) triggered increases of up to 10–20 times depending on the strain.

The finding provides insight into how antimicrobial resistance (AMR) evolves and spreads under agricultural conditions.

Estimates suggest that 70% of all antibiotics worldwide are used in farm animals, not people. Antibiotics can be given to animals as growth promoters or to prevent infections rather than to treat sick animals. While these practices are banned in the UK, and UK farming has significantly reduced antibiotic usage in the past decade, this is not the case in other parts of the world. These findings raise concerns about the environmental impact of antibiotic residues from farming and human wastewater. Even concentrations too weak to stop bacterial growth could accelerate the spread of resistance genes that make infections harder to treat.

Dr Charlotte Gray-Hammerton, Postdoctoral Research Associate at the Ineos Oxford Institute for antimicrobial research and first author of the paper said: "We tend to think only high doses of antibiotics are dangerous, but our results show that even small amounts left in the environment, for example, from animal treatments or waste, can help bacteria share their resistance genes much more easily.

"Antibiotic resistance isn't just a hospital problem- it's an environmental one too. Our work shows how bacteria in farms can act as gene reservoirs, and how small antibiotic traces could amplify their spread."

Building on this study, the team plans to expand their research to include long-term monitoring of antibiotic resistance in agricultural environments, particularly those where antibiotic use is high. They aim to identify how specific environmental pressures such as sublethal antibiotic exposure shape the evolution and transfer of resistance genes.

These findings pave the way for future research into how we can disrupt these transfer mechanisms in the environment. Understanding the precise conditions that promote resistance spread will help us develop better strategies for monitoring and mitigating AMR. Our next steps are to explore how environmental factors, like farm management practices or antibiotic residues, influence these genetic exchanges over time.

The findings from the research emphasise that minimal antibiotic exposure can drive resistance highlighting the need for responsible antibiotic use and integrated global monitoring to combat this growing public health threat.

Read the full paper here: Frontiers | Sublethal concentrations of antibiotics enhance transmission of antibiotic resistance genes in environmental Escherichia coli

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