In the face of rising antibiotic resistance, bacteriophage therapy has re-emerged as a promising alternative. However, bacteria can rapidly evolve resistance to phages, threatening the long-term success of such treatments. A new review published in Current Molecular Pharmacology delves into the molecular mechanisms behind bacterial resistance and outlines adaptive strategies to overcome it.
The authors detail how bacteria employ diverse defenses, including surface receptor modification, restriction-modification systems, CRISPR-Cas immunity, and biofilm formation. “Bacterial defenses impose heavy costs on bacteria but also pose a significant challenge to phage therapy’s long-term success,” said lead author Sahar Karamlou. The ongoing co-evolutionary arms race between phages and bacteria drives rapid adaptation, necessitating dynamic therapeutic approaches.
To counter resistance, the review highlights several promising strategies. Phage cocktails targeting multiple bacterial receptors can reduce the emergence of resistant mutants. Engineered phages with enhanced host ranges and depolymerase enzymes help penetrate biofilms. Combining phages with antibiotics leverages synergistic effects to improve efficacy and reduce resistance rates. Additionally, computational and AI-driven models are enabling more precise phage selection and personalized treatment designs.
“The combination of integrated molecular, clinical, and regulatory innovations is essential to advance phage therapy as a sustainable solution against multidrug-resistant infections,”said corresponding author Zeinab Mohsenipour. As research progresses, these multifaceted approaches offer hope in turning phage therapy into a reliable clinical option for the post-antibiotic era.