16
Oct
Combination of Pesticide and Nitrogen Use in Agriculture Escalates the of Spread Antibiotic-Resistant Bacteria
(Beyond Pesticides, October 16, 2025) An important new study links pesticides, antibiotics, and nitrogen fertilizers to the extreme global crisis of antibiotic resistance, raising serious concerns about the adverse impacts of conventional (chemical-intensive) agricultural practices. The research team, from several Chinese universities and laboratories and Queen’s University in Belfast, conducted a three-year study in China using soil bacteria and phages (bacteriophages, or viruses that invade bacteria) from an experimental field, exposing them to a variety of conditions ranging from the control (no exposures) to various combinations of nitrogen fertilizer and two categories of pesticides (the insecticide chlorpyrifos and a blend of the fungicides azoxystrobin and propiconazole).
Phages are viruses that eat bacteria. They invade the bacterial cell and, in various ways, cause the death of the bacterium. Some viral genes cause the cells to lyse, or dissolve, releasing their genetic material into the surrounding environment, where other organisms can pick up new genes. In this way, phages are a major pipeline for horizontal gene transfer (movement of genes in bacteria from one bacterial species to another) among microbes. This phenomenon is of increasing concern because the genes circulating in this marketplace include many that enhance antibiotic resistance.
The researchers were interested in whether the combination of nitrogen and pesticide mixtures affected the transfer and use of antibiotic-resistance genes (ARGs). The ARGs of most concern are those that are highly mobile, pathogenic, and resident in human environments.
They found a number of remarkable associations:
- In a particularly novel and significant finding, the researchers found that nitrogen was a strong driver of resistance processes. The richness and diversity of the phages were highest in the groups exposed to both nitrogen and combined pesticides, and the abundance of ARGs in phages was “markedly elevated†in those same exposure conditions. They also observed higher abundance of auxiliary metabolic genes, including those associated with virulence and gene transporters, under those conditions. The abundant presence of the ARGs and the auxiliary genes indicates that both viruses and bacteria are trying to survive under adverse conditions. They are at least in part responses to challenges to human-made soil inputs.
- The researchers found 41 high-risk ARGs, about a quarter of the total number of ARGs. The high-risk genes included those conferring resistance to tetracycline and bacitracin, and two genes for multidrug resistance.
- The number of high-risk ARGs in the group exposed to the highest levels of mixed pesticides plus nitrogen was more than three times the number in the control group.
- The phages found in the various test groups included those found in the human gut, forest soils, tundra and permafrost, and deep-sea sediments. Some of the phage types overlapped these environments, indicating the widespread occurrence of phages with the potential to distribute resistance genes to microbes.
The influence of nitrogen fertilizers adds an important dimension to the role of agricultural practices in generating antibiotic resistance. Nitrogen benefits some soil microbes, but it is a stressor for many others. It increases ARG abundance and can enhance uptake of the heavy metals cadmium and copper by crops. Other effects include reducing enzyme activity and acidifying the soil.
The problem of antibiotic resistance, like the resistance of target organisms to pesticides, is an urgent global phenomenon. The pharmaceutical industry has not been able to keep up with the inevitable development of microbial resistance by developing new antibiotics. One expert defined the antibiotic era as lasting from the 1930s, when sulfa drugs were introduced, to 2005, when daptomycin was introduced. Daptomycin is a last-resort treatment for resistant bacterial infections, such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci. Resistance to daptomycin has been reported clinically and in a Staphylococcus strain common in industrial pig farms. In fact, a 2021 study found the resistance gene in multiple geographically distant species and traced its origin to the pig microbe, showing how horizontal gene transfer in microbes can distribute genes far and fast, and how industrial agriculture threatens food security worldwide.
The use of antibiotics as pesticides has contributed to the resistance problem. Currently EPA has registered only three antibiotics for application to crops, mostly for use on fruits, some tree nuts, a few vegetables, and some ornamentals. The antibiotic streptomycin has been used as a pesticide against greening on Florida citrus crops. In 2021, Beyond Pesticides joined with other groups in a lawsuit against EPA to stop the practice, and the Ninth Circuit Court of Appeals ruled in the plaintiffs’ favor in 2023, saying EPA had not shown that streptomycin would be effective or that the agency had taken steps to protect against the emergence of resistance. EPA could have and should have known. As one review in 2024 put it, “In almost every region where streptomycin has been used to control bacterial diseases in the United States, bacterial populations resistant to this antibiotic have been detected.†Beyond Pesticides continues to urge EPA to cancel all uses of a pesticide when resistance is discovered or considered likely based on its chemical structure.
But in addition to using antibiotics as pesticides, pesticides can trigger resistance to antibiotics all by themselves. Beyond Pesticides’ July 11 Daily News reports on a study from India finding that glyphosate, 2,4-D, and dicamba help bacteria become resistant to tetracycline and ampicillin; previous research has shown that these pesticides create resistance in Salmonella and E. coli. The Indian study also found that chlorpyrifos increases the circulation among microbes of multidrug-resistant plasmids, and azoxystrobin strengthens Pseudomonas aeruginosa’s ability to pump threatening molecules like antibiotics and pesticides out of its cells. P. aeruginosa causes many hospital-acquired infections and is highly resistant to many antibiotics.
The situation with bacteriophages is made more complex by another and increasingly popular idea to cope with the resistance crisis: that these phages could be used to combat multidrug-resistant bacteria.
They do, after all, attack and kill bacteria. The idea was first proposed in 1917 but ignored in favor of antibiotics until the recent resistance crisis, except in the former Soviet Union and its satellite countries. In the U.S., there is increasing interest as more desperate cases of bacterial infection failing to respond to any antibiotics or combinations thereof arise in the medical system.
Phages are far more selective than antibiotics, attacking specific types of bacteria rather than killing off entire microbiota, but this means scientists must search through thousands of phages to find the ones effective against a particular bacterium. Yet at the same time, while there is a risk that the bacteria will become resistant to the attacking phages, in some cases, that resistance has made the bacteria more sensitive to antibiotics.
Suffice it to say that phage therapy against resistant microbes is in its infancy, and in any case, does not directly address the interactivity of pesticides, antibiotics, and nitrogen fertilizers in the agricultural system. While it may prove beneficial in clinical settings, the crisis in these settings is the end result of the vast uncontrolled use of both antibiotics and industrial chemicals, such as pesticides and fertilizers in the ambient environment. Both antibiotics and pesticides are notoriously misused around the world, and without removing both from agriculture, there is no control over how living organisms—bacteria and viruses comprising the vast majority of these – will make use of the resulting opportunities.
The Organic Foods Production Act does not allow the use of synthetic nitrogen fertilizers or antibiotics and restricts the use of synthetic chemicals–including pesticides–to those on the National List of Allowed and Prohibited Substances. Allowed materials on the National List must be approved by the National Organic Standards Board, based on a finding that they are not harmful to humans or the environment, necessary for organic production and handling, and consistent with organic practices.
Pesticides, antibiotics, and climate change are a triple threat to humanity and the biosphere. Every interaction between pesticides and antibiotics – and, it is now known, nitrogen fertilizers – that increases microbial resistance raises the threat of new pandemics that cannot be controlled.
All unattributed positions and opinions in this piece are those of Beyond Pesticides.
Sources:
Combined pesticide pollution enhances the dissemination of the phage-encoded antibiotic resistome in the soil under nitrogen deposition
Shen et al
PNAS October 2025
https://pubmed.ncbi.nlm.nih.gov/41042849/
Court Finds EPA Allowance of Antibiotic Streptomycin Use on Citrus Illegal
Beyond Pesticides, December 20, 2023
https://beyondpesticides.org/dailynewsblog/2023/12/court-finds-epa-allowance-of-antibiotic-streptomycin-use-on-citrus-illegal/
Adding to Wide Body of Science, Study Finds Pesticide Residues Threaten Health of Soil Microbiome
Beyond Pesticides, May 13, 2025
https://beyondpesticides.org/dailynewsblog/2025/05/adding-to-wide-body-of-science-study-finds-pesticide-residues-threaten-health-of-soil-microbiome/
Exploring Bacteriophage Therapy for Drug-Resistant Bacterial Infections
Schooley Robert T
Bacteriophages March 2023
https://www.iasusa.org/wp-content/uploads/2023/03/31-1-23.pdf
National Organic Standards
Beyond Pesticides
https://www.beyondpesticides.org/programs/organic-agriculture/keeping-organic-strong/national-organic-standards
Phage Therapy: Past, Present and Future
Madeline Barron
American Society for Microbiology 2022
https://asm.org/articles/2022/august/phage-therapy-past,-present-and-futures
