Bacteriophages: A Therapy Concept against Multi-Drug–Resistant Bacteria

Abstract

Bacteriophages (phages) are viruses that kill bacteria specifically but cannot infect other kinds of organisms. They have attracted new attention since the increasing antibiotic resistance developed into a global crisis. Phage therapy, a 100-year-old form of antibacterial treatment in medicine, is gaining momentum because phages represent a therapy concept without such negative side effects as toxicity; phages are the only therapeutic agent that regulates itself at the sites of infection and decays when the infectious bacteria have been killed. Nature is an almost infinite phage resource: New ones can be isolated for most kinds of problem bacteria as needed; bacteria and their phages constantly co-evolve. This is important as new pathogenic bacterial variants evolve and new challenging situations arise. In human therapy, “cocktails” of multiple phages may reduce the probability of selecting bacteria that developed resistance to a certain phage. Antibiotic agents can be applied together with phages in many circumstances; the two often function synergistically. Phages cannot be expected to replace antibiotic agents in our medical arsenal, but can be used where antibiotic agents fail. The selected phages, however, must be obligately virulent, well-characterized, and highly purified before application. Countless patients and their physicians are waiting for re-establishing phage therapy as a flexible, tailored medicine; infrastructures should be built in all countries urgently: The 2015 World Health Organization assembly resolution 68.7.3. called for national action plans by May 2017 to combat the antimicrobial drug resistance crisis. This article discusses the therapeutic potential of phages and describes challenges and recent developments.

The global preclinical antibacterial pipeline

“…Phage therapies have garnered a lot of attention lately due to the successful treatment of a small number of individual patients with chronic conditions limited to a small number of experimental treatment centres, often in compassionate use programmes 10,41,42 . Compassionate use of personalized phage preparations is limited to specific clinical circumstances and individual physicians and researchers who have experience with phage therapy 42 .…”

An exegesis of bacteriophage therapy: An emerging player in the fight against anti-microbial resistance

“…While standardized cocktails would be convenient, due to regional specificity of phage action (already described), their outcomes may differ across geographical regions; while the resources needed for production of customized phage cocktails are considerable, and have been regarded by some to be unsustainable. Rohde et al [6] , argue that bacteria resistance to bacteriophages is an unsustainable concept, for several reasons. First being the fact that the mechanism of resistance of microbes to bacteriophages, involves evolutionary mutations, which can be mimicked by phages to counter the development of resistance.…”

“…Despite his being the first to make the discovery, due to paucity of funds and his enlistment in the Royal Army, Frederick Twort was unable to further his research [3] , a situation well capitalized upon by d'Herelle, who went on to carry out several non-randomized clinical trials of phage therapy all over the world, the results of which he captured in a 1931 report in the bulletin of the New York Academy of Medicine [5] . Félix d'Herelle eventually, through his collaboration with Georgian scientist George Eliava, established the Eliava Institute of Bacteriophage Microbiology and Virology (IBMV) in Tbilisi, Georgia in 1933, a facility that has developed into one of the most reputable bacteriophage therapy research centers in the world [6] . However, most of their works were written in Russian, and even after being translated into English, many of the results were rejected by the Western world as they were perceived to incompliant with international standards of safety [7] .…”

In-Gel Isolation and Characterization of Large (and Other) Phages

“…We note that, for phage therapy, the various screens do not have to be perfect. In modern-day practice, phage therapy is already effective with screening only for lytic character [66][67][68]. In any case, phage therapy is done with cocktails of several phages that are not likely to all have the same disadvantages.…”