Author: Dr. Paul Lawrence, Executive Director of Research and Discovery | Biocogent, LLC
Abstract:
The cosmetic care industry has embraced the revolution in skin microbiome research, doggedly pursuing new platforms to effectively modulate the populations of microbes on the skin. These advances also coincide with the potentially catastrophic increase in microbes resistant to multiple anti-microbial measures. As such, efforts to modulate the skin microbiome dovetail with endeavors to identify alternative solutions to countering antibiotic resistance. Currently, the best studied option is bacteriophage therapy (or simply “phage therapy”), a technology that predates the advent of antibiotics and is based on biology dating back nearly 4 billion years.
Two scientists, Felix d’Herelle and Frederick Twort, from the World War I era co-discovered biological agents that d’Herelle termed “bacteriophages”: viruses that uniquely target and lyse bacteria in a species-specific and sometimes strain-specific manner. Not long after, phages were explored for their capacity to ameliorate a variety of bacterial diseases with enough success that large-scale commercialization was pursued by major drug and cosmetic companies in the US and Europe. However, by the mid-1940s, phage therapy was supplanted by the development of the first antibiotic drugs. The only nations that continued investigating the utility of phage therapy were the former Soviet Union, Georgia, and Poland. With the modern dilemma of antibiotic resistance, the rest of the globe has reinitiated their phage studies with several achievements, particularly in the prevention of food borne illnesses from contaminating bacteria like such as Escherichia coli and Listeria monocytogenes.
Here, we report the findings of our ongoing investigation into using phage therapy to mitigate skin conditions caused by Staphylococcus aureus such as pressure ulcers and atopic dermatitis. A phage hunt was commissioned to find no less than three unique phages capable of countering S. aureus growth. This was a much more complicated effort than prior work with Cutibacterium acnes targeted phages as S. aureus exhibits greater genetic diversity and as such, all newly discovered phage needed to be tested against multiple strains of S. aureus. To that end, three unique S. aureus targeted phages were collected and characterized that lysed and suppressed the growth of multiple strains of that bacterium. Genetic sequencing and structural imaging by transmission electron microscopy revealed that one of the isolated phages was a Podoviridae member and the other two were Myoviridae. The capacity of the individual phage preparations to target and diminish five S. aureus strains was evaluated by both optical density (OD) measurements of laboratory cultures and efficiency of plaquing (EOP) assay. These experiments demonstrated that all three phages were capable of countering S. aureus growth within 24 hours, though depending upon the strain, some were inhibitory to bacterial growth while others engaged in a full lytic cycle. These studies were extended to evaluate the impact of the phages on biofilms produced from three different strains of the bacterium, which further reinforced their efficacy in a dose-dependent manner.
The next step in the phage investigation involved two different reconstituted human epidermal models: one infused with S. aureus and the other with Staphylococcus epidermidis. These skin tissue models were employed to evaluate the three-phage cocktail for tolerable use levels as well as was for its capacity to diminish the bacteria growth levels in a species-specific manner. The absence of an impact on the S. epidermidis model confirmed the combination’s narrow effect on S. aureus without collateral damage on the skin microbiome. Furthermore, at the conclusion of the S. aureus skin model study, the tissue was examined for changes in the expression levels of 93 different skin-relevant genes.
In conclusion, phage therapy represents an exciting new methodology for precisely modulating the skin microbiota in an effort to improve skin health with precision targeting of specific microbes. This platform is highly effective at reducing the targeted bacterial species without negatively impacting potentially beneficial neighboring species. The topical application of a formulation infused with the phage cocktail will deliver a one-two punch of countering one of the root causes of pressure ulcers and atopic dermatitis.
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