Biological foundations of successful bacteriophage therapy

Abstract

Bacteriophages (phages) are selective viral predators of bacteria. Abundant and ubiquitous in nature, phages can be used to treat bacterial infections (phage therapy), including refractory infections and those resistant to antibiotics. However, despite an abundance of anecdotal evidence of efficacy, significant hurdles remain before routine implementation of phage therapy into medical practice, including a dearth of robust clinical trial data. Phage-bacterium interactions are complex and diverse, characterized by coevolution trajectories that are significantly influenced by the environments in which they occur (mammalian body sites, water, soil, etc.). An understanding of the molecular mechanisms underpinning these dynamics is essential for successful clinical translation. This review aims to cover key aspects of bacterium-phage interactions that affect bacterial killing by describing the most relevant published literature and detailing the current knowledge gaps most likely to influence therapeutic success.

Alternatives Therapeutic Approaches to Conventional Antibiotics: Advantages, Limitations and Potential Application in Medicine

“…The first phage activity dated back to 1896, when Ernest Hankin reported that the waters from the rivers Ganges and Yamuna in India possessed antibacterial activity against Vibrio cholerae [ 69 ]. In the late 1910s, and following initial work by the English bacteriologists Ernest Hankin and Frederick Twort, a French microbiologist from the Pasteur Institute (Felix d’Herelle, 1917) identified viruses that specifically and selectively parasitized bacteria and named them “bacterium eaters” (bacteriophages) [ 70 , 71 ]. It was d’Herelle who first developed the notion of using phages therapeutically to treat bacterial infection with encouraging results [ 69 ].…”

Bacteria common to rhizosphere communities of Asiatic bittersweet across a post-glacial landscape

“…One possible means of reducing unwanted bacteria is to use taxa specific phages to reduce their numbers. Phage therapy is being used in medicine to treat human pathogens (Pirnay et al, 2022;Venturini et al, 2022) and more recently to control plant pathogens (Ye et al, 2019). Unfortunately, the bacteria associated here with Asiatic bittersweet can be beneficial to other plants in this ecosystem therefore it may not be reasonable to eliminate them.…”

Biomimetic Bacteriophage‐Like Particles Formed from Probiotic Extracts and NO Donors for Eradicating Multidrug‐Resistant Staphylococcus aureus

“…[ 14 ] Similar strategies include bacteriophage therapy, in which bacterial viruses are used to infect drug‐resistant bacteria and induce lysis, [ 15 ] but although it has been reported that the introduction of living microorganisms can have an excellent antibacterial effect, controllability and biosafety still need to be considered. [ 16 ]…”

“…[14] Similar strategies include bacteriophage therapy, in which bacterial viruses are used to infect drug-resistant bacteria and induce lysis, [15] but although it has been reported that the introduction of living microorganisms can have an excellent antibacterial effect, controllability and biosafety still need to be considered. [16] To our knowledge, combining the advantages of probiotics and NO to design a safe and efficient method of infected wound healing has rarely been discussed, and no practical way to simultaneously avoid all the potential problems in treating infected wounds has been reported. Therefore, a facile and broadly applicable strategy is necessary to realize the combination of low-risk probiotics and low-dosage NO for antibacterial treatment.…”