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bioRxiv · 10.1101/2025.07.25.666796

Plasmids link antibiotic resistance genes and phage defense systems in E. coli

Slesak, W. A.·Jedryszek, P.·Cazares, D.·Matlock, W.·MacLean, C.
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Abstract

Phage therapy has been proposed as an alternative to antibiotics to treat resistant infections. However, we have a limited understanding of how antibiotic resistance genes (ARGs) associate with bacterial phage defense systems (PDSs). Here, we explore the relationship between ARGs and PDSs in a sample of 2,559 plasmids originating from 1,044 E. coli isolates, representing a snapshot of clinical and non-clinical diversity in Oxfordshire, UK (2008-2020). In total, we identify 3,193 ARGs and 14,013 PDSs (180 unique types). We demonstrate that E. coli plasmids are enriched for ARGs and PDSs (both p<0.001), with a bias towards toxin-antitoxin/abortive-infection, TIR-domain and CBASS systems (all q<0.025). We proceed to show that ARGs and PDSs are physically linked by plasmids (p<0.001). Together, our results suggest that phage therapy may inadvertently select for antibiotic resistant bacteria, and that antibiotic use may similarly drive resistance to phage.

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Slesak, W. A., Jedryszek, P., Cazares, D., Matlock, W., MacLean, C.. 2025-07-27. Plasmids link antibiotic resistance genes and phage defense systems in E. coli. https://doi.org/10.1101/2025.07.25.666796

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