Antibiotic resistance genes are often portrayed as a modern medical problem driven by the overuse of antibiotics in hospitals and farms. A new comprehensive review published in Biocontaminant reveals a much deeper and more complex story. Antibiotic resistance is an ancient feature of microbial life, shaped by millions of years of evolution and strongly influenced by today's human activities that connect natural environments, animals, and people.
The study, led by researchers at Hohai University in China, examines where antibiotic resistance genes come from, why they persist in nature, and how human actions are accelerating their movement into disease causing bacteria. Framed through a One Health perspective, the review highlights the tight links between environmental health, animal health, and public health.
"Antibiotic resistance did not begin with modern medicine," said corresponding author Guoxiang You. "Many resistance genes originally evolved to help bacteria survive environmental stresses, long before humans discovered antibiotics. The real danger today comes from how human activities are breaking down natural barriers and allowing these genes to spread into pathogens."
The authors explain that many resistance genes are derived from ordinary bacterial genes with essential physiological roles, such as pumping out toxic substances or transporting nutrients. Over evolutionary time, these genes gained the ability to defend against antibiotics as a secondary function. In undisturbed ecosystems like soils, lakes, and remote environments, most resistance genes remain locked within specific microbial communities and pose little risk to human health.
A key reason for this containment is genomic incompatibility. Bacteria that are genetically very different often cannot easily exchange and use resistance genes. This natural mismatch acts as a biological firewall, limiting the spread of resistance across species and habitats.
However, human activity is weakening this firewall.
The review highlights how agriculture, wastewater discharge, urbanization, and global trade increase connectivity between environments that were once separate. Antibiotics used in medicine and livestock create strong selection pressures, while manure application, wastewater reuse, and environmental pollution bring together bacteria from soil, animals, and humans. These conditions make it easier for resistance genes to jump into disease causing microbes.
"Human driven habitat connectivity changes everything," said lead author Yi Xu. "When bacteria from different environments are repeatedly brought into contact under antibiotic pressure, resistance genes that were once harmless can become a serious public health threat."
Wastewater treatment plants are identified as critical hotspots, where high bacterial densities and residual antibiotics promote gene exchange. Agricultural soils fertilized with manure can also act as bridges, allowing resistance genes to move from livestock into environmental bacteria and eventually back to humans through food, water, or direct contact.
Importantly, the authors stress that not all resistance genes are equally dangerous. High abundance in the environment does not automatically mean high risk. Understanding which genes are mobile, compatible with human pathogens, and linked to disease is essential for effective monitoring and control.
The review calls for ecosystem centered strategies to combat antibiotic resistance. These include reducing unnecessary antibiotic use, improving wastewater treatment technologies, managing manure and sludge more carefully, and protecting relatively pristine ecosystems that serve as baselines for natural resistance levels.
"Antibiotic resistance is not just a medical issue," You said. "It is an ecological problem rooted in how we interact with the environment. Protecting antibiotics for future generations requires protecting ecosystem integrity today."
By integrating evolutionary biology, microbial ecology, and environmental science, the authors argue that a One Health approach offers the most realistic path forward in addressing one of the greatest global health challenges of our time.
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Journal reference: Xu Y, Wang J, Fu T, Yang S, You G, et al. 2025. Evolutionary origins, ecological drivers, and environmental implications of antibiotic resistance genes proliferation and dissemination: a 'One Health' perspective. Biocontaminant 1: e014
https://www.maxapress.com/article/doi/10.48130/biocontam-0025-0014
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About Biocontaminant :
Biocontaminant is a multidisciplinary platform dedicated to advancing fundamental and applied research on biological contaminants across diverse environments and systems. The journal serves as an innovative, efficient, and professional forum for global researchers to disseminate findings in this rapidly evolving field.
