Bacteriophages as a viable therapeutic alternative to standard antibiotics
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Launching C-CAMP’s AMR Quest 2023 soon! A nation-wide search to identify India’s top innovative solutions in AMR. Watch this space for more details.
In the quest of discovering alternative therapies for consistently evolving antibiotic-resistant pathogens, phage therapy has emerged as a potent candidate. There has been renewed interest in developing phage therapy over the last few years. This is because of the high efficiency and precision that phage therapy offers in managing multi-drug resistance pathogens.
What are bacteriophages?
Bacteriophages are ubiquitous viral entities present in nature that specifically target bacteria. Phages are prominently known to influence innate immunity by interacting with the immune system. Based on the lifecycle bacteriophages can be classified as lytic or temperate. Lytic phages are used in phage therapies as they infect host cells (bacteria) and eventually kill them.
Origin & history
Ernest Hanbury Hankin, an eminent bacteriologist observed effective antibacterial properties against cholera in the Ganga and Yamuna rivers in India. Following his work in 1915, British bacteriologist Fredrick Twort encountered an agent that showed bactericidal and bacteriostatic properties. However, his research was overlooked due to the ongoing First World War [RB1] and discovery and mass production of antibiotics.
Phage therapy was re-discovered in the former Soviet Republic, with an aim to test the efficacy and safety to treat bacterial infection. However, the data were inaccessible to Western scientists and antibiotics led the world with fast-acting results, easy storage, and regulation.
The need for ‘ecosystem of innovative therapeutics’ required to deal with antibiotic resistance
Antibiotic consumption has only seen an increase ever since its discovery. Implementation of conventional antibiotic treatments resulted in the emergence of antimicrobial resistance (AMR).[RA2] The natural phenomenon of adaptations, mutation, and transfer of cross-resistance traits in microbes was accelerated due to the overreliance on antimicrobials as the sole treatment option for infections.
An innovative approach and rediscovery of therapeutics are now required to control AMR bacterial infections and spread. Phage therapy sets an ideal example of an alternative modality to treat critical AMR cases.
However, the well entrenched nature of the ecosystem of antibiotics also forms a kind of epistemological infrastructure, which acts as a powerful inhibitor to the development of phage therapy.
Bacteriophage therapy as a potential treatment for the ‘Invisible pandemic of AMR’
Therapeutic efficacy of phage cocktails reemerged as a potential treatment after complete oblivion until the end of the 20th century. Redevelopment of phage therapy saw renewed push due to their biocidal competence against ‘superbugs.’ Bacteriophages also show synergistic potential to treat critical immunosuppressed patients.
Clinical trials of bacteriophage therapy have proven to be safe and effective for treatment of various health conditions such as chronic ear infection, infected wounds, urinary tract infections, burns, cystic fibrosis-associated lung infections and other AMR-related conditions. In 2015, [RA3] an intravenous phage cocktail resulted in the complete recovery of a patient suffering from MDR Acinetobacter baumannii.
Possible advantages and limitations associated with bacteriophages
Advantages
· Specifically target the infection causing agent thus preserving the good microbes which contribute to a healthy gut
· Ideal to control infections caused by AMR pathogens and disrupt bacterial biofilms
· Exhibit narrower chances to induce resistance
Limitations
· Standard regulatory practices are not in place
· Phage selection for a specific resistant trait is difficult
· Lack of demonstrated success of phage therapy in all phases of clinical trials
· Research and development framework are based on the mainstream drug economy
The case to promote phage research
Bacteriophages can be developed to treat clinical pathogenic bacteria in humans, animals, and crops as well as nonpathogenic bacteria responsible for degradation of food products. Thus, phage therapy has applications in the human clinical as well as food, and livestock industry. Other than treatment of human diseases bacteriophages can enhance and act as a natural biocontrol agent.
FDA and USDA have been allowing the use of phages to safeguard food products from spoilage from bacteria. FDA has approved LISTEX-a phage product against Listeria monocytogenes to enhance the shelf life of cheese. Phage products targeted against pathogens like Vibrio, Aeromonas and others, to increase shelf life of fish from are also being promoted.
Global contribution to develop bacteriophage as a weapon against AMR
Antibiotic resistance is a health emergency worldwide, that requires collaborative and preventive measures to treat deadly infections. Innovative approaches to mitigate multi-drug resistance pathogens with precise results are need of the hour. Phage therapy can be one such alternative, but the ecosystem required to push phage research is not as well developed as other alternatives. Entities like CARB-X and C-CAMP are supporting research and innovators in this sector. For example, Phico Therapeutics, Locus Biosciences and SNIPR Biome are currently supported by CARB-X for the development of potential phage treatments and preventatives against MDR infections. [RB4] [RA5] While [RA6] C-CAMP supported research has resulted in identification of N4-like bacteriophage with activity against several multidrug-resistant clinical Pseudomonas aeruginosa isolates.
Standardization of clinical trials for phage products, a dedicated push for fundamental research to better understand pharmacokinetics of phages, applied research to ensure efficacy and safety will help to increase market authorization of market ready phage formulations. This [BR7] will result in phage therapy becoming a mainstream therapeutic technology to tackle infections in general and AMR infections in particular.
Disclaimer: The blog is a compilation of information on a given topic that is drawn from credible sources; however, this does not claim to be an exhaustive document on the subject. The mention of entities, networks, consortiums, or partnerships is merely to highlight the stakeholders working in the field and does not reflect attestations, validations or promotion of their work. It is not intended to be prescriptive, nor does it represent the opinion of C-CAMP or its partners. The blog is intended to encourage discussion on an important topic that may be of interest to the larger community and stakeholders in associated domains.
Sources:-
1) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3442826/
2) https://www.nature.com/articles/s41599-020-0478-4
3) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5905571/
4) https://www.sciencedirect.com/science/article/pii/S2214799320300849
5) https://www.labiotech.eu/trends-news/micreos-phages-listeria/
6) https://carb-x.org/gallery/phico-therapeutics/
7) https://carb-x.org/gallery/locus-biosciences/
8) https://carb-x.org/gallery/snipr-biome-aps/[RB8]
[RB1]Which World War?
should this be defined here as (AMR) since that abbreviation is then used below? [RA2]
should be “an intravenous….”? [RA3]
[RB4]Richard and Trudy, can you review for accuracy?
I added “currently” [RA5]
Not sure what this sentence is trying to convey, but as written “while” does not fit at the start.
[BR7]Check this part of the sentence
[RB8]Added reference for SNIPR Biome
