Phage Therapy in Clinical Practice: Treatment of Human Infections

Abstract

Phage therapy is the application of bacteria-specific viruses with the goal of reducing or eliminating pathogenic or nuisance bacteria. While phage therapy has become a broadly relevant technology, including veterinary, agricultural, and food microbiology applications, it is for the treatment or prevention of human infections that phage therapy first caught the world's imagination--see, especially, Arrowsmith by Sinclair Lewis (1925)--and which today is the primary motivator of the field. Nonetheless, though the first human phage therapy took place in the 1920s, by the 1940s the field, was in steep decline despite early promise. The causes were at least three-fold: insufficient understanding among researchers of basic phage biology; over exuberance, which led, along with ignorance, to carelessness; and the advent of antibiotics, an easier to handle as well as highly powerful category of antibacterials. The decline in phage therapy was neither uniform nor complete, especially in the former Soviet Republic of Georgia, where phage therapy traditions and practice continue to this day. In this review we strive toward three goals: 1. To provide an overview of the potential of phage therapy as a means of treating or preventing human diseases; 2. To explore the phage therapy state of the art as currently practiced by physicians in various pockets of phage therapy activity around the world, including in terms of potential commercialization; and 3. To avert a recapitulation of phage therapy's early decline by outlining good practices in phage therapy practice, experimentation, and, ultimately, commercialization.

Contrasted coevolutionary dynamics between a bacterial pathogen and its bacteriophages

“…Most studies of bacteria-phage coevolution involve the model system Pseudomonas fluorescens SBW25 and its lytic phage ϕ2 (15). Although these studies are important for an in-depth understanding of this process, their restriction to a single host-parasite pair is unfortunate, given the immense diversity of bacteria and phages in both terrestrial and aquatic ecosystems (26)(27)(28) and the importance of many of these organisms in human health (29). Thus, the generality of previous results to other bacterial species and to different phages parasitizing a given bacterium remains an open question.…”

Rapid evolution of generalized resistance mechanisms can constrain the efficacy of phage–antibiotic treatments

“…One alternative strategy to antibiotics is phage therapy: the use of parasitic viruses that specifically infect and kill certain bacterial pathogens. Compared to antibiotics, phage therapy is more targeted, leaving the beneficial or commensal microbiota unharmed (Skurnik, Pajunen, & Kiljunen, 2007), self‐replicating at the target site during the course of an infection (Carlton, 1999), efficient against antibiotic‐resistant bacteria (Kutter et al., 2010) and has low inherent toxicity to humans (Abedon & Thomas‐Abedon, 2010). Furthermore, phages have the distinct advantage of being able to evolve with the bacteria to regain infectiveness via a coevolutionary arms race (Betts, Vasse, Kaltz, & Hochberg, 2013; Friman et al., 2016; Scanlan, Buckling, & Hall, 2015).…”

Antimicrobial bacteriophage-derived proteins and therapeutic applications

“…(For history of phage therapy see refs. [3][4][5][6]. Phages have remarkable bacteriostatic and bacteriolytic activity as part of their natural lytic lifecycle, by first disrupting the bacterium's metabolism to produce new virus particles, then lysing the host cell to release the progeny.…”