Bacteriophage therapeutics in the era of antimicrobial resistance: Precision biological control of multidrug resistant Escherichia coli

Abstract

Antimicrobial resistance (AMR) is a growing global health crisis that threatens the effectiveness of modern medicine and compromises the management of infectious diseases. Among resistant pathogens, multidrug-resistant (MDR) Escherichia coli is of particular concern due to its widespread ecological distribution, genetic adaptability, and role in both community and healthcare-associated infections. MDR E. coli is frequently implicated in urinary tract infections, bacteremia, enteric diseases, and systemic infections, while also serving as a reservoir for transferable resistance genes across clinical, veterinary, food, and environmental settings within the One Health framework. The declining efficacy of conventional antibiotics has renewed interest in bacteriophages (phages) as targeted antibacterial agents. Phages are viruses that specifically infect bacteria and exhibit unique features such as host specificity, self-replication at infection sites, and bactericidal activity through lytic mechanisms. Unlike broad-spectrum antibiotics, phages selectively eliminate target bacteria without significantly disrupting commensal microbiota and act independently of classical antibiotic targets, enabling activity against resistant strains. This review synthesizes ecological, molecular, evolutionary, and translational insights into phage-based strategies against MDR E. coli. Advances in phage isolation, genomic characterization, and structural biology have improved understanding of host range, infection dynamics, and safety. However, challenges remain, including bacterial resistance to phages, immunological interactions, pharmacokinetics, regulatory considerations, and large-scale manufacturing. Emerging innovations such as engineered phages, phage-derived lysins, and combination therapies further expand therapeutic potential. Continued multidisciplinary research is essential to translate phage therapy into sustainable clinical and veterinary applications against AMR.