Bacteriophages with their inate ability to target bacteria could be of interest for treating biofilms in the clinical setting.
Bacteria growing in layers, or biofilms, are often highly resistant to antibiotics and are capable of surviving in very harsh environments. Treating biofilm-related infections is a major challenge for doctors today.
Bacteriophages, or ‘phages’ for short are viruses that kill bacteria. Phage therapies are now being re-evaluated as a complementary treatment that can synergise antibiotic treatments. Unlike antibiotics, phages are specific and only kill particular types of bacteria. Co-treatments of phages and antibiotics promise to reduce the development of resistance in bacteria and extend the useful life of the antibiotics that are currently available. Because data on their efficacy is still being collected, phages are currently used only for patients where other therapeutics have failed.
Antibiotic resistance is a major global health crisis and has led to renewed interest in phage therapy. The preferred clinical modality is to pair phages with an antibiotic, to target bacteria for which there are limited, or no therapeutic options.
Phages and antibiotics could also be used interchangeably. When bacteria are defending themselves against phages they may become less aggressive as pathogens, or To date, only a few studies have evaluated the synergistic relationship between phages and antibiotics (Morrisette et al., 2020); Chegini et al., 2020). One study has shown that establishing a phage infection in the biofilm prior to antibiotic exposure achieved the greatest reductions in the biofilm (Kumaran et al., 2018). Using this approach will reduce the emergence of antibiotic resistance during therapy. In-vitro studies have highlighted that the order of treatment greatly affects biofilm eradication outcomes.
While there have been many in-vivo studies on the efficacy of phage therapy alone, few studies have compared in-vivo efficacy of phages directly with individual or multiple antibiotics. In order to accurately quantify phage efficiency more research is necessary using a biofilm model to optimise these interactions and the order of treatment. These studies will provide information on the most appropriate phages for treatment of clinical biofilms, either alone or in combination with antibiotics.
However, one application that has already proven to be successful is based on Listeriaphage P100, which was produced to eliminate biofilms present in processed meat products and on factory working surfaces. It has already been authorised for use in the United States by the Department of Agriculture.#
The primary limitation of phage treatments is their ability to access and target bacterial cells inside the biofilm due to presence of the glue-like extracellular material, which acts as a physical obstacle to phage diffusion. However, some phages possess exopolysaccharide depolymerases which enhances the phage invasion and dispersion process through the biofilm under treatment.
Further Reading on bacteriophages
Chegini, Z., Khoshbayan, A., Taati Moghadam, M., Farahani, I., Jazireian, P. and Shariati, A. (2020) ‘Bacteriophage therapy against Pseudomonas aeruginosa biofilms: a review’, Annals of Clinical Microbiology and Antimicrobials, vol. 19(45), https://doi.org/10.1186/s12941-020-00389-5.
Kumaran, D., Taha, M., Yi, Q., Ramirez-Arcos, S., Diallo, J.S., Carli, A. and Abdelbary, H. (2018) ‘Does Treatment Order Matter? Investigating the Ability of Bacteriophage to Augment Antibiotic Activity against Staphylococcus aureus Biofilms’, Frontiers in Microbiology, vol. 9, https://doi.org/10.3389/fmicb.2018.00127.
Morrisette, T., Kebriaei, R., Lev, K.L., Morales, S. and Rybak, M.J. (2020) ‘Bacteriophage Therapeutics: A Primer for Clinicians on Phage-Antibiotic Combinations’, Pharmacotherapy, vol. 40(2), pp. 153-168 https://doi.org/10.1002/phar.2358.
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