The spread of antibiotic resistance genes poses a serious and global public health threat. A new comprehensive review by Hohai University scientists explores the evolutionary origins, environmental factors underlying the spread and spread of antibiotic resistance genes, and their far-reaching environmental consequences.
The evolution of antibiotic resistance genes is associated with intrinsic physiological roles and environmental differences. Image credit: Xu etc.., two: 10.48130/biocontam-0025-0014.
Antibiotic resistance genes have become one of the most serious global public health threats as their spread spans interconnected areas of humans, animals and the environment.
They have been found in some of the most extreme and pristine environments on Earth, including the depths of the Mariana Trench, pristine Alaskan soil and 30,000-year-old permafrost deposits, places completely untouched by man-made antibiotics.
This widespread distribution confirms an important truth: these bacterial species evolved the ability to tolerate antibiotics millions of years before the production of antibiotics for clinical and agricultural applications.
“Antibiotic resistance did not originate in modern medicine,” said Dr. Guoxiang Yu, an author of the study.
“Many resistance genes originally evolved to help bacteria survive environmental stresses, long before humans discovered antibiotics.”
“The real danger today comes from how human activity breaks down natural barriers and allows these genes to spread into pathogens.”
“Many resistance genes are derived from common bacterial genes that perform important physiological functions, such as the clearance of toxic substances or the transport of nutrients,” the researchers say.
“Over time, these genes acquired the ability to protect themselves from antibiotics as a secondary function.”
In undisturbed ecosystems such as soils, lakes and remote areas, most resistance genes remain locked into specific microbial communities and pose little risk to human health.
“The main reason for this containment is genomic incompatibility,” they added.
“Bacteria that are genetically very different often cannot easily exchange and use resistance genes.”
“This natural disparity acts as a biological firewall, limiting the spread of resistance between species and habitats.”
“However, human activity weakens this firewall.”
In the review, the authors highlight how agriculture, wastewater discharge, urbanization, and global trade are increasing connectivity between environments that were once separate.
Antibiotics used in medicine and animal husbandry create strong selection pressures, while manure application, wastewater reuse, and environmental pollution combine bacteria from soil, animals, and humans.
These conditions facilitate the penetration of resistance genes into pathogenic microbes.
“Human-managed habitat connectivity changes everything,” said Dr. Yi Xu, first author of the study.
“When bacteria from different environments are repeatedly exposed to antibiotics, resistance genes that were once harmless can become a serious public health threat.”
“Wastewater treatment plants are considered critical hotspots where high bacterial densities and antibiotic residues promote gene exchange.”
“Agricultural soils fertilized with manure can also act as bridges, allowing resistance genes to move from livestock to environmental bacteria and ultimately back to humans through food, water or direct contact.”
It is important to note that scientists emphasize that not all resistance genes are created equal.
High abundance in the environment does not automatically mean high risk.
Understanding which genes are mobile, compatible with human pathogens, and associated with disease is essential for effective monitoring and control.
Researchers are calling for ecosystem-based strategies to combat antibiotic resistance.
These include reducing unnecessary antibiotic use, improving wastewater treatment technologies, better manure and sludge management, and protecting relatively intact ecosystems that serve as the basis for determining natural levels of resistance.
“Antibiotic resistance is not just a medical problem,” Dr. Yu said.
“This is an environmental problem rooted in how we interact with the environment.”
“Protecting antibiotics for future generations requires protecting the integrity of ecosystems today.”
“By integrating evolutionary biology, microbial ecology and environmental science, the One Health approach offers the most realistic path forward in addressing one of the greatest global health challenges of our time.”
review was published online on December 5, 2025 in the journal Biopollutant.
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Yi Xu etc.. 2025. Evolutionary origins, environmental drivers, and ecological consequences of the spread and spread of antibiotic resistance genes: a One Health perspective. Biopollutant 1: e014; two: 10.48130/biocontam-0025-0014
