Abstract
Bacteriophages (simply referred to as Phages) are a class of viruses with the ability to infect and kill prokaryotic cells (bacteria), but are unable to infect mammalian cells. This unique ability to achieve specific infectiousness by bacteriophages has been harnessed in antibacterial treatments dating back almost a decade before the antibiotic era began. Bacteriophages were used as therapeutic agents in treatment of dysentery caused by Shigella dysenteriae as far back as 1919 and in the experimental treatment of a wide variety of other bacterial infections caused by Vibrio cholerae, Staphylococcus sp., Pseudomonas sp. etc, with varying degrees of success. Phage therapy and its many prospects soon fell out of favour in western medicine after the Second World War, with the discovery of penicillin. The Soviet Union and other countries in Eastern Europe however mastered the craft of bacteriophage isolation, purification and cocktail preparation, with phage-based therapeutics becoming widely available over-the-counter. With the recent rise in cases of multi-drug resistant bacterial infections, the clamour for a return to phage therapy, as a potential solution to the anti-microbial resistance (AMR) crisis has grown louder. This review provides an extensive exposé on phage therapy, addressing its historical use, evidences of its safety and efficacy, its pros and cons when compared with antibiotics, cases of compassionate use for treating life-threatening antibiotic-resistant infections, the limitations to its acceptance and how these may be circumvented.
Highlights
The birth, rise and fall of the bacteriophage therapy conceptBacteriophages are a group of viruses with the ability to infect bacteria without posing any threat to human host tissues or disturbing significantly the normal flora
anti-microbial resistance (AMR) is a consequence of horizontal transfer of anti-microbial resistant genes (ARG) between bacteria, due to excessive use of antibiotic agents in human medicine as well as animal agriculture
A further advantage of the mutatory mechanisms of resistance to phages by bacteria was elucidated by Chan et al [111], who reported that due to efforts to develop resistance to a lytic bacteriophage OMKO1, which targets surface receptor OprM for binding, mutations in OprM, restored antibiotic sensitivity in multi-drug resistant Pseudomonas aeruginosa strains, in an evolutionary trade-off
Summary
Bacteriophages are a group of viruses with the ability to infect bacteria without posing any threat to human host tissues or disturbing significantly the normal flora. In 1915, Frederick Twort, a British microbiologist had described certain transparent organisms small enough to pass through filters with mesh sizes capable of trapping most bacteria [3] It would be Félix d’Herelle, a French microbiologist who first described these organisms by the name: ‘bacteriophages’ and conceived the idea of using them therapeutically for the treatment of bacterial infections. 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] 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]. This fact, coupled with the boom in commercial development of antibiotics in the 1940s led to the widespread abandonment of phage therapy in the Western world [8], but not in Russia and Eastern Europe, due to the initial unavailability of antibiotics in the former Soviet Union [9,10]
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