26 SEP TEMBER 2022 • WORLD AQUACULTURE • WWW.WA S .ORG What are Bacteriophages? Bacteriophages are the oldest and most numerous organisms on the planet. Based on epifluorescence microscopy, it was suggested that there are at least ten phages for each bacterial cell present in the environment. Over the last 50 years, more than 5100 bacteriophages have been identified and studied, with over 90 percent of them belonging to the Myoviridae, Siphoviridae and Podoviridae families, characterized by the possession of a head and a tail. There are over 25,000 complete bacteriophage genomes in the NCBI database (2022), evidence of the renewed interest in these organisms. Bacteriophages (Fig. 1) usually possess a protein head, also called a capsid, containing their genetic material. It is attached to a contractile tail that usually ends with six tail fibers connected by a base plate. These fibers contain the receptor-binding proteins responsible for recognizing and attaching to specific molecules on the surface of the targeted bacterial membrane. Figure 2 is a transmission electron micrograph of Bacteriophage T4, active against E. coli bacteria. Most phages range between 25 and 200 nm in length and, in this case, the different components can be clearly seen in the photograph. How They Work Once bacteriophages use their tail fibers to attach to the cell surface, they inject their DNA into the bacterial cell. At this point, two lifecycles can be distinguished: lysogenic and lytic. For the bacteriophage to be virulent and be instantly effective against bacterial cells, it needs to undergo a lytic cycle. This means that, once injected, its DNA and proteins will synthesize and assemble into virions that will multiply until ultimately causing cell lysis. The virions are then released into the host’s organism to repeat the process with other bacterial cells. Proteon’s products are made exclusively with virulent phages to ensure efficacy of the product (Fig. 3). Alternatively, if the phage undergoes a lysogenic cycle, its DNA integrates with the bacterial chromosome by recombination and the lysogenic bacterium reproduces normally. Only occasionally and in specific conditions does the phage DNA excise from the bacterial chromosome and enter a lytic cycle. These bacteriophages are not desirable for commercial solutions because lysis of pathogens cannot be guaranteed. Proteon Pharmaceuticals: WhoWe Are and HowWe Use Bacteriophages Proteon Pharmaceuticals is a Polish company that has been developing bacteriophage feed additives for the animal production industry for over ten years. It is currently operating in Asia, Africa and Middle East, with commercially ready products for the poultry and aquaculture industries. We hold multiple patents, have developed a proprietary production methodology and been given many awards and grants for our work. Our mission is to eliminate antibiotics from the food chain and consequently improve animal and human health. Our products are cocktails of bacteriophages. The combination of different, synergistic phages increases the product’s ability to strengthen the immune system and help control pathogenic bacteria. When developing a new product, we first identify and characterize FIGURE 4. BAFADOR® a cocktail targeting Aeromonas spp. and Pseudomonas spp. FIGURE 3. Lytic lifecycle of bacteriophages.
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