Bacteriophage therapy
use of phages. 21 Beginning with the case of Alfred Gertler, who suffered from a severe methicillin- resistant Staphylococcus aureus infection and was successfully treated at the Eliava Institute in 2001, 22 a new drive for the revival of phage therapy emerged amid the worsening global AMR crisis with advanced gene sequencing technology and a more comprehensive understanding of phages’ mode of action. In fact, according to Patey et al. (2018), the therapeutic use of phages was never completely abandoned in the west as phage research proceeded and phage therapy had been occasionally used as biotechnological tools in the agri-food sector and as therapeutic agents in exceptional cases when antibiotics failed. In 2017, a successful application of intravenous phage therapy against Acinetobacter baumannii on compassionate grounds in the United States was reported and was subsequently regarded as a critical turnaround in the course of the development of phage therapy in Western medical systems. 23 In England, a 15-year-old cystic fibrosis (CF) patient with a disseminated drug-resistant Mycobacterium abscessus infection was cured by a three-phage cocktail with natural and engineered phages in the following year. 24 Modern cutting-edge technology also endows phages with new therapeutic potentials, for example, as a promising approach for cancer therapy. 25 With an escalating number of start-up companies worldwide focusing on therapeutic phages, ongoing clinical trials, phage-related scientific publications (e.g., genetics, immunology and pharmacology) and more importantly, a deteriorating situation of AMR, increasing attention has been given to nature’s secret weapon, bacteriophages, from both the public and the wider scientific community. Without the slightest shadow of doubt, as the new dawn nears us, we are currently standing on a critical point of the redevelopment of phage therapy.
For a detailed timeline of phage therapy, refer to Appendix I – A Timeline of Phage Therapy.
On the unique biology of phages
Bacteriophages are bacterial viruses that specifically target and infect viruses as their hosts and are generally non-pathogenic (i.e., harmless) to human cells. Phages are believed to be the most ubiquitous and diverse life-like biological entities on the Earth, with an estimated more than 10 31 phages present (there are about 10 23 stars in the known universe) in the biosphere at this very moment. Although the average length of a typical phage is assumed to be 100 nm, if all phages on this planet were gathered and connected from head to tail, the length of the line would exceed 10 20 kilometres or 10 million light- years, which is equivalent to 7,850,000,000,000,000 times the diameter of the Earth’s equator (Suttle, 2013). With up to 70% of marine bacteria being infected by phages, 26 their ubiquitous presence and the unique predator-prey relationship indicate the non-negligible role played by phages in the natural evolution of bacteria. As bacteria mutate to develop resistance against phages and ‘escape’ from phage predation, phages promptly evolve even at a more rapid rate as a countermeasure to overcome the new resistance and, consequently, stabilize the former predator-prey relationship. 27 Therefore, from an evolutionary ecological perspective, the long-lasting antagonistic co-evolutionary dynamic patterns between bacteria and phages 28 are indeed a potential vault of significant biological value which may ultimately
21 Brives & Pourraz 2020. 22 Häusler 2008.
23 Schooley et al. 2017. 24 Dedrick et al. 2019. 25 Pranjol & Hajitou 2015; O’Hare 2019. 26 Prescott et al. 1993. 27 Comeau & Krisch 2005. 28 Williams 2009.
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