Using models of vertical inheritance and horizontal transfer, they found that low doses of tetracycline, ampicillin, kanamycin, and streptomycin stabilize resistance and promote gene transfer across species. Mechanistic analyses reveal increased oxidative stress, membrane permeability, and ATP production as drivers, while modeling predicts that long-term exposure to such low-level antibiotics leads to faster and more persistent expansion of resistant bacteria.
Antibiotic resistance is a major global health threat, contributing to an estimated 1.27 million deaths annually and projected to cause 39 million deaths by 2050. Two pathways accelerate the spread of antibiotic resistance genes (ARGs): vertical gene transfer (VGT), where resistance is inherited during cell division, and horizontal gene transfer (HGT), which includes conjugation, transformation, and phage-mediated exchange. Although antibiotics are known drivers of resistance, their environmental concentrations—often far below clinical minimum inhibitory concentrations (MICs)—remain poorly understood in terms of long-term, real-world effects on bacterial evolution. Given that more than 90% of consumed antibiotics are excreted unmetabolized and widely enter natural ecosystems, understanding how low-level residues shape resistance dynamics is an urgent research priority.
A study (DOI:10.48130/biocontam-0025-0005) published in Biocontaminant on 07 November 2025 by Yue Wang’s & Jie Wang’s team, Tiangong University, demonstrates that even low, environmentally relevant concentrations of antibiotics can significantly accelerate the persistence and spread of antibiotic resistance genes through both vertical inheritance and horizontal gene transfer.
To investigate how environmentally relevant antibiotics affect the spread and stability of ARGs, the researchers established a 10-day vertical transmission system, complemented by mathematical modeling, to predict long-term shifts in plasmid-carrying versus plasmid-free bacteria. They also constructed intra- and intergeneric conjugation systems and a transformation model using Acinetobacter baylyi and plasmid pWH1266 to assess HGT under low-dose exposure, while applying RT-qPCR, ROS assays, membrane permeability tests, ATP measurements, and HPLC to probe underlying mechanisms. Results showed that kanamycin, ampicillin, and streptomycin increased resistant bacteria and stabilized resistance over time, whereas tetracycline slowed early growth but still maintained resistance, partly due to bacterial degradation detected by HPLC. MIC measurements confirmed stable or enhanced resistance, with streptomycin inducing new cross-resistance. Gene expression analyses demonstrated strong upregulation of tolC, oxyR, soxR, recA, ompA, and ompC, linking ROS accumulation and membrane remodeling to persistent ARG inheritance. Modeling revealed that, without antibiotics, plasmid-free bacteria dominate, but under antibiotic pressure, plasmid-bearing strains expand and persist. Conjugation and transformation assays further showed that low-dose antibiotics (0.005–5 mg/L) boosted plasmid transfer and transformation by up to fivefold through elevated ROS, increased membrane permeability, higher ATP, and activation of conjugation genes, whereas high doses suppressed HGT by reducing ATP and cell viability. Modeling confirmed that such low-level antibiotics accelerate long-term HGT and increase overall transformant abundance.
The findings highlight a critical but often overlooked environmental challenge: even trace antibiotic pollution can substantially accelerate both the inheritance and exchange of resistance genes. This means that treated wastewater, agricultural runoff, aquaculture systems, and hospital discharge waters may act as hotspots that amplify resistance spread, even when antibiotic concentrations are far below therapeutic levels. By demonstrating that sub-MIC antibiotic residues enhance both VGT and HGT, the study suggests that environmental exposure thresholds and discharge standards may require re-evaluation. Improved surveillance of antibiotic residues and mitigation strategies will be essential to contain the environmental drivers that fuel the global rise of antibiotic resistance.
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References
DOI
10.48130/biocontam-0025-0005
Original Source URL
https://doi.org/10.48130/biocontam-0025-0005
Funding information
This study was financially supported by the National Natural Science Foundation of China (Nos. 42307529 and 42577486), Hebei Natural Science Foundation (Nos. C2023110006 and E2023110001), the Research Fund of Tianjin Key Laboratory of Aquatic Science and Technology (No. TJKLAST-PT-2021-04), and Cangzhou Institute of Tiangong University (No. TGCYY-F-0103).
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.