A game of resistance: War between bacteria and phages and how phage cocktails can be the solution
Pedro Costa, Carla Pereira, Jesús L. Romalde, Adelaide Almeida
Abstract
While phages hold promise as an antibiotic alternative, they encounter significant challenges in combating bacterial infections, primarily due to the emergence of phage-resistant bacteria. Bacterial defence mechanisms like superinfection exclusion, CRISPR, and restriction-modification systems can hinder phage effectiveness. Innovative strategies, such as combining different phages into cocktails, have been explored to address these challenges. This review delves into these defence mechanisms and their impact at each stage of the infection cycle, their challenges, and the strategies phages have developed to counteract them. Additionally, we examine the role of phage cocktails in the evolving landscape of antibacterial treatments and discuss recent studies that highlight the effectiveness of diverse phage cocktails in targeting essential bacterial receptors and combating resistant strains. • Phages can be an alternative in combating bacterial infections. • The emergence of phage-resistant bacteria hinders the effectiveness of phage therapy. • Bacterial defense mechanisms reduce the effectiveness of phage therapy. • Phage cocktails can overcome the challenges posed by bacterial defenses. • This review examines how phage cocktails can be effective against bacterial defenses.