Genetic compatibility and ecological connectivity drive the dissemination of antibiotic resistance genes
Journal article, 2025
The dissemination of mobile antibiotic resistance genes (ARGs) via horizontal gene transfer is a significant threat to public health globally. The flow of ARGs into and between pathogens, however, remains poorly understood, limiting our ability to develop strategies for managing the antibiotic resistance crisis. Therefore, we aim to identify genetic and ecological factors that are fundamental for successful horizontal ARG transfer. We used a phylogenetic method to identify instances of horizontal ARG transfer in similar to 1 million bacterial genomes. This data was then integrated with >20,000 metagenomes representing animal, human, soil, water, and wastewater microbiomes to develop random forest models that can reliably predict horizontal ARG transfer between bacteria. Our results suggest that genetic incompatibility, measured as nucleotide composition dissimilarity, negatively influences the likelihood of transfer of ARGs between evolutionarily divergent bacteria. Conversely, environmental co-occurrence increases the likelihood, especially in humans and wastewater, in which several environment-specific dissemination patterns are observed. This study provides data-driven ways to predict the spread of ARGs and provides insights into the mechanisms governing this evolutionary process.
Author
David Lund
Chalmers, Mathematical Sciences, Applied Mathematics and Statistics
University of Gothenburg
Marcos Parras Moltó
Chalmers, Mathematical Sciences, Applied Mathematics and Statistics
University of Gothenburg
Juan Salvador Inda Diaz
University of Gothenburg
Chalmers, Mathematical Sciences, Applied Mathematics and Statistics
Stefan Ebmeyer
University of Gothenburg
Chalmers, Life Sciences, Systems and Synthetic Biology
D. G. Joakim Larsson
University of Gothenburg
Anna Johnning
Chalmers, Mathematical Sciences, Applied Mathematics and Statistics
University of Gothenburg
Fraunhofer-Chalmers Centre
Erik Kristiansson
Chalmers, Mathematical Sciences, Applied Mathematics and Statistics
University of Gothenburg
Nature Communications
2041-1723 (ISSN) 20411723 (eISSN)
Vol. 16 1 2595The Environment as a Driver of Antibiotic Resistance (EDAR)
Swedish Research Council (VR) (2018-05771), 2019-01-01 -- 2024-12-31.
The diversity and mobility of novel antibiotic resistance genes
Swedish Research Council (VR) (2019-03482), 2020-01-01 -- 2023-12-31.
Subject Categories (SSIF 2025)
Bioinformatics (Computational Biology)
Microbiology
Evolutionary Biology
DOI
10.1038/s41467-025-57825-3
PubMed
40090954
Related datasets
Results from "Genetic compatibility and ecological connectivity drive the dissemination of antibiotic resistance genes" by Lund et al. [dataset]
URI: https://doi.org/10.5281/zenodo.14901409