40 - Phage

Bacteriophages -- viruses that target and kill bacteria -- were one of the most promising medical treatments of the early 20th century, and were used to treat all sorts of infections, from cholera to staph, and everything in between. But by the 1950s, they had all but died out in the West. This episode tells the story of the humble phage, from its discovery in the waters of the Ganges, love trysts ending in a KGB execution, and to a resurgence of this once forgotten therapy in the 21st century as an answer to antibiotic resistance. Sources:   Abedon ST, Bacteriophage prehistory: Is or is not Hankin, 1896, a phage reference? Bacteriophage. 2011 May-Jun; 1(3): 174–178. Blair JE and Williams REO, “Phage Typing of Staphylococci,” Bull Org mond. Ste, 1961, 24, 771-784. Davis BM and Waldor MK, Filamentous phages linked to virulence of Vibrio cholera, Current Opinion in Microbiology 2003, 6:35-42. d’Herelle F, “Bacteriophage as a treatment in acute medical and surgical infections,” Bull N Y Acad Med. 1931 May; 7(5): 329–348. d'Herelle F.  Sur un microbe invisible antagoniste des baccilles dysenteriques.  CR Acad Sci Paris 1917,163,173-5. Eaton MD, Bayne-Jones S. Bacteriophage Therapy. JAMA 1934; 103:1769-76; 1847-53; 1934-9. Fruciano DE and Bourne S, Phage as an antimicrobial agent: d’Herelle's heretical theories and their role in the decline of phage prophylaxis in the West, Can J Infect Dis Med Microbiol. 2007 Jan; 18(1): 19–26 Hankin EH.  L'action bactericide des eaux de la Jumna at du Gange sur le vibrion du cholere. Ann Int Pasteur (Paris) 1896,10,511-23. Himmelweit F. Combined action of penicillin and bacteriophage on Staphylococci. Lancet. 1945;ii:104. Hicks DJ et al, “Developments in rabies vaccines,” Clin Exp Immunol. 2012 Sep; 169(3): 199–204. Kingwell K, Bacteriophage therapies re-enter clinical trials, Nature, Vol 14, Aug 2015, 515. Jensen MA et al, Modeling the role of bacteriophage in the control of cholera outbreaks, Proc Natl Acad Sci U S A. 2006 Mar 21; 103(12): 4652–4657. Hargreaves KR and Clokie MRJ, Clostridium difficile phages: still difficult? Front Microbiol. 2014 Apr 28;5:184. La Fee S and Buschman H, Novel Phage Therapy Saves Patient with Multidrug-Resistant Bacterial Infection. Retrieved from: https://health.ucsd.edu/news/releases/Pages/2017-04-25-novel-phage-therapy-saves-patient-with-multidrug-resistant-bacterial-infection.aspx Leitner L et al, Bacteriophages for treating urinary tract infections in patients undergoing transurethral resection of the prostate: a randomized, placebo-controlled, double-blind clinical trial. BMC Urol. 2017 Sep 26;17(1):90. Pearce J, Louis Pasteur and Rabies: a brief note, Journal of Neurology, Neurosurgery & Psychiatry 2002;73:82. Schooley et al, Development and use of personalized bacteriophage-based therapeutic cocktails to treat a patient with a disseminated resistant acinetobacter baumannii infection. Antimicrobial Agent and Chemotherapy, 14 Aug 2017. Strathdee S, How Sewage Saved My Husband's Life from a Superbug, TEDxNashville, retrieved from: https://www.youtube.com/watch?v=AbAZU8FqzX4. Summers WC, Bacteriophage Therapy, Annual Review of Microbiology, Vol. 55:437-451 (Volume publication date October 2001) Summers WC, The strange history of phage therapy. Bacteriophage. 2012 Apr 1; 2(2): 130–133. Taylor M.W. (2014) Introduction: A Short History of Virology. In: Viruses and Man: A History of Interactions. Springer, Cham Thiel, K. (2004). Old dogma, new tricks—21st Century phage therapy. Nature Biotechnology, 22(1), 31–36. Twort FW, An investigation on the nature of Ultra-Microscopic Viruses, The Lancet, Jan 10th, 1914. 101. Wittebole X et al, A historical overview of bacteriophage therapy as an alternative to antibiotics for the treatment of bacterial pathogens. Virulence. 2014 Jan 1; 5(1): 226–235. Ujmajuridze et al, Adapted Bacteriophages for Treating Urinary Tract Infections. Front Microbiol. 2018; 9: 1832. Ventola CL, “The Antibiotic Resistance Crisis: Part 1: Causes and Threats,” P T. 2015 Apr; 40(4): 277–283.