A brief history about the superheroes: the bacteriophages

Bacteriophages (phages) are viruses of the bacteria which have the capability to infect and kill bacteria. Based on their life-cycle, they are classified into lytic and temperate phages. The history of works relating to bacteriophages dates back to the year 1896 where an English chemist Ernest Hankin reports the bactericidal activity of waters collected from the Indian rivers Jumna and Ganga on Vibrio cholerae [1]. Twenty years later, the discovery of the bacteriophages was credited to two independent researchers, an English microbiology Fedrick Twort in 1915 [2] and a French Canadian microbiology Felix d’Herelle in 1917 [3] who observed a filterable and transmissible agent that caused the bacterial lysis. The term “bacteriophage” was coined by Felix d’Herelle [4]. Initially, d’Herelle tested the efficacy of the suspension on himself, his friends, and family, and then he gave it to patients suffering from dysentery and cholera. Since then, he focused on investigating other infections relating to Salmonella, Shigella, Pasteurella, etc.. The first report on the phage therapy was published in 1921 [5]. A review by Richard Sharp summarises the biology and history of the bacteriophages wherein; he elucidated the initial report by Hankin to the early interest by the medical and industrial sector in pursuing bacteriophages, the development of molecular understandings such as the experiments by Hershey and Chase on the validation of nucleic acid to be the genetic material and discoveries of Salvador Luria and his colleagues on the replication mechanism of the phages, finally he concludes on the isolation and characterization of the bacteriophages [6]. William Summers has complied with the early works of literature on phage therapy [7], and Altamirano, F.L.G., and Barr, J.J (2019) have covered the key points to consider for successful phage therapy in the post-antibiotic era [8].

Since the discovery of phages, the curiosity to study its therapeutic potential grew in an exponential way to several nations such that in 1932 bacteriophages were used extensively to control cholera outbreaks in India [9]. Later few pharmaceutical companies in France and the USA, such as L’Oréal [10] and Eli Lilly Company, produced commercial phage preparations, a review paper has summarised the companies involved in bacteriophage-based preparations [11]. The discovery of antibiotics by Alexander Fleming in 1928 led to the downfall of bacteriophages, especially in the Western world [11]. Although in the demise of bacteriophage research in the antibiotic era, few Eastern nations such as Poland, Georgia, and Russia continued the phage research and it is still in practice. In 1923, Georgian microbiologist George Eliava constituted a dedicated institution for phage therapy and its research entitled Eliava Institute of Bacteriophage, Microbiology, and Virology in Tbilisi, Georgia. In the last three decades, there has been a void in the discovery of antibiotics, and due to the misuse and overuse of the antibiotics the bacteria have acquired resistance to multiple antibiotics, this is causing severe problems in almost all sectors right from aquaculture, environment, food, etc., Owing to this frightening concern, researchers all over the world are searching for alternative therapies to combat these deadly superbugs while the incident rates of resistant infections are on the rise.

In these hard-times, bacteriophage-based therapy seems convincing based on the preliminary studies, and its re-emergence has been the saviour of people’s lives. Two of the critical studies in treating drug-resistant infections in recent times have spurred the interest in pursuing this in clinical scale. In 2015, a patient with multi-drug resistant infection was successfully treated with bacteriophages in San Diego, California [12]. In another instance, a 15-year old patient with a double lung transplant contracted with a Mycobacterium infection, and all the antibiotics failed to clear the infection while three bacteriophages were recombinantly engineered to eradicate them successfully [13].

In conclusion, the bacteriophages are natural rivals of the bacteria and have been evolving since its inception. Even though its potential was concealed during the antibiotic era, the recent problems due to the antibiotic resistance infections have made us look back and re-discover its inherent ability to combat the deadly pathogens. Studies must be encouraged towards learning their capability in the clinical setting as an alternative strategy to fight a war against the untreatable micro-organisms that are resistant to antibiotics.

References

[1] Hankin, E., 1896. The bactericidal action of the waters of the Jumna and the Ganges on Vibrio cholerae. Ann Inst Pasteur, 10, p.511.

[2] Twort, F.W., 1921. THE ULTRA-MICROSCOPIC VIRUSES. The Lancet, 198(5108), p.204.

[3] d’Herelle, M.F., 1961. Sur un microbe invisible antagoniste des bacilles dysentériques. Acta Kravsi.

[4] Duckworth, D.H., 1976. ” Who discovered bacteriophage?”. Bacteriological reviews, 40(4), p.793.

[5] d’Herelle, F. and LeLouet, G., 1921. Sur la vaccination antibarbonique par virus atténué. CR Soc. Biol. Paris, 85, pp.1011-13.

[6] Sharp, R., 2001. Bacteriophages: biology and history. Journal of Chemical Technology & Biotechnology, 76(7), pp.667-672.

[7] Summers, W.C., 2001. Bacteriophage therapy. Annual Reviews in Microbiology, 55(1), pp.437-451.

[8] Altamirano, F.L.G. and Barr, J.J., 2019. Phage therapy in the postantibiotic era. Clinical microbiology reviews, 32(2), pp.e00066-18.

[9] Morison, J., 1932. Bacteriophage in the Treatment and Prevention of Cholera. Bacteriophage in the Treatment and Prevention of Cholera.

[10] Summers, W.C., 1999. Felix dHerelle and the origins of molecular biology. Yale University Press.

[11] Monk, A.B., Rees, C.D., Barrow, P., Hagens, S. and Harper, D.R., 2010. Bacteriophage applications: where are we now?. Letters in applied microbiology, 51(4), pp.363-369.

[12] Schooley, R.T., Biswas, B., Gill, J.J., Hernandez-Morales, A., Lancaster, J., Lessor, L., Barr, J.J., Reed, S.L., Rohwer, F., Benler, S. and Segall, A.M., 2017. Development and use of personalized bacteriophage-based therapeutic cocktails to treat a patient with a disseminated resistant Acinetobacter baumannii infection. Antimicrobial agents and chemotherapy, 61(10), pp.e00954-17.

[13] Dedrick, R.M., Guerrero-Bustamante, C.A., Garlena, R.A., Russell, D.A., Ford, K., Harris, K., Gilmour, K.C., Soothill, J., Jacobs-Sera, D., Schooley, R.T. and Hatfull, G.F., 2019. Engineered bacteriophages for treatment of a patient with a disseminated drug-resistant Mycobacterium abscessus. Nature medicine, 25(5), pp.730-733.

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