Therapeutic potential of phages and phage products combats multidrug resistant bacteria

Abstract

Inappropriate and excessive deployment of antimicrobial agents across human medicine, livestock, and agricultural settings constitutes the primary catalyst for the proliferation of multidrug-resistant (MDR), extensively drug-resistant (XDR), and pandrug-resistant (PDR) microbial strains. This phenomenon, known as Antimicrobial Resistance (AMR), severely compromises the management of these infections by diminishing the pool of effective treatment modalities, which consequently raises the risk of lethal consequences. The ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species), identified by the World Health Organization (WHO) as multidrug-resistant (MDR) agents causing hospital-acquired infections, require the urgent development of novel, efficacious treatments. The therapeutic landscape is further complicated by challenges posed by colistin- and carbapenem-resistant Gram-negative bacteria, along with vancomycin-resistant strains of S. aureus (VRSA) and E. faecium (VRE). The problem of Antimicrobial Resistance (AMR) in animal agriculture is magnified by scarce antimicrobial options and slow R&D. Consequently, there has been an increased focus on bacteriophages—viruses that precisely destroy bacteria and their protective biofilms. Phage cocktails are gaining attention as they provide more accurate infection control and show potential to limit the proliferation of antibiotic resistance better than therapies using a single phage. Moreover, phages and their derived enzymes (endolysins) are effective in substantially decreasing foodborne contaminants. This review focuses on the promising role of bacteriophages in clinical and applied settings. It outlines their potential in treating MDR pathogen infections observed in animal models and reports on relevant clinical studies conducted on both humans and animals. The review gives special attention to the collaboration between phages and conventional antibiotics (synergy), and how phages contribute to safer food production. A significant part of the discussion is dedicated to identifying and resolving current challenges to bolster therapeutic performance of bacteriophage agents.