1. Introduction
Bacteriophages, or phages, are viruses that infect and replicate within various bacteria and do not carry the potential to infect eukaryotic cells [1]. There are an estimated 1031 phages; their near-ubiquitous distribution partly facilitates the astonishing abundance of these infectious agents. Bacteriophages exist wherever there are bacteria and are therefore found in nearly every environmental matrix as well as in animal and human guts [2,3,4,5]. The viruses that comprise the realm of phages have each evolved to rely on specific bacterial hosts for survival. The molecular machinery of these hosts facilitates the proliferation of the phage, in some cases sufficiently disrupting metabolic processes, leading to bacterial lysis and death [5]. This ability of phages to exploit bacteria provides an exciting tool for combating pathogenic bacteria. The therapeutic potential of bacteriophages has therefore garnered worldwide attention in the last few years, offering promising applications in combatting difficult-to-treat bacterial infections when antibiotics fail.
Bacteriophages were discovered in the early 20th century, and their therapeutic utility for treating certain infections was acknowledged shortly thereafter [6,7,8]. The logistics of phage research presented considerably greater practical challenges than antibiotic development, and the original studies evaluating phage therapy in clinical settings yielded statistically insignificant or questionable findings. As favorable and scalable outcomes were achieved from antibiotic research, antibiotics swiftly monopolized the market and gained investment by large pharmaceutical companies, tipping the scales away from phage development. Several political and social issues also contributed to a diminished interest in phage research. World War II and the Cold War fostered a global landscape in which novel discoveries were not readily shared between the United States (U.S.), the Soviet Union (USSR), and their respective allied nations. As a result, while antibiotic research and production boomed across most high-income countries (HICs), the USSR continued to prioritize bacteriophage therapy [9]. Antibiotic discovery, research, and production throughout the 20th century made antibiotics the cornerstone of bacterial disease management while phage research and therapeutic development dwindled into relative obscurity.
Antibiotics have served as a cornerstone of modern medicine for most of the past century. Bacterial infections, however, continue to cause substantial loss of life and health across the world, disproportionately impacting lower-middle-income countries (LMICs) which are nations with a gross national income per capita of less than USD 4125 [10,11]. The widespread and excessive utilization of antibiotics in medical and agricultural settings has contributed to rapidly evolving antimicrobial resistance (AMR) to many of the therapeutics developed over the past eighty years [12]. Growing resistance to this method of combating infection has challenged the clinical utility of even the most efficacious antibiotics. Those species of bacteria posing the gravest threat to the efficacy of antibiotics today include Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter faecium, collectively known as the ESKAPE pathogens [13]. These pathogens are known to subvert the antimicrobial action of the most widely available antibiotics. With the escalating threat of AMR, bacteriophage therapy has returned to the forefront as a potential tool to mitigate a rapidly worsening global health crisis.
In this review, we discuss the current state of bacteriophage research—phage discovery, classification, and production. We describe the potential therapeutic application of phages, particularly regarding their use in addressing antibiotic-resistant infections. We also review challenges of developing new drugs to combat AMR and emphasize the importance of international collaboration in phage research and industrial production.
