03 November 2022 - Antimicrobial resistance is a serious threat to both human and animal health. The global animal production industry is being called to reduce its use of antibiotics to avoid contributing to the further development of resistance by bacterial populations.
However, the animal production industry is itself under pressure from bacterial pathogens, and cannot simply accept the higher mortality and lower productivity that microbes such as Salmonella, Escherichia coli, and Clostridium perfringens impose. A solution is therefore needed which does not contribute to the development of antimicrobial resistance.
Global animal nutrition company Pathway Intermediates believes that bacteriophages can provide that solution. Alongside their R&D partner Optipharm, they have been developing and updating bacteriophage cocktails for swine and poultry production. Today, we hear from Dr. Hyunil Kim, CEO of Optipharm, and Mr. Kenneth Seo, Director of Pathway Intermediates’ International Sales Division, about how bacteriophages work to keep bacteria under control, and about how the companies plan to help bring awareness of this solution to the wider world.
[Feedinfo] Let’s start with a brief introduction to the concept of bacteriophages. Why is there less chance of bacteria developing resistance to bacteriophages compared to an antibiotic? By what mechanism do they destroy their target bacteria?
[Dr. Hyunil Kim] The word “bacteriophages” means “something that eats bacteria.” Bacteriophages have a unique mechanism that gives a strong bactericidal property. This mechanism starts by attaching to the surface of targeted bacteria after recognizing specific receptors or proteins on the cell membrane. Next, bacteriophages inject their DNA into the targeted bacteria and make more than 100 replicates. These bacteriophage replicates then rupture out from the targeted bacteria, killing them. Afterwards, these replicates go on to repeat the process.
Regarding the question of antibiotic resistance: while an antibiotic contains non-specific or broad spectrum of antimicrobial effects against bacteria, bacteriophages have host specificity. In other words, they recognize only the targeted bacteria, and kill the targeted bacteria with a unique mode of action. Moreover, once the targeted bacteria bursts, it is impossible to regenerate. This unique mode of action makes bacteriophages less vulnerable to the possibility that resistance might develop against them.
[Feedinfo] Can you talk about the history of research in bacteriophages at Optipharm and Pathway Intermediates? How and when did the two begin collaborating on this subject?
[Dr. Hyunil Kim] Optipharm has not only the best R&D department but also the top animal disease diagnosis center in South Korea. The animal disease diagnosis department currently holds over 70% of the market share in the field. This diagnostic technology and system gives Optipharm the ability to identify disease outbreaks and develop related solutions. Since 2011, Optipharm has been studying bacteriophages in order to provide solutions to the animal industry. Thereafter, we joined forces with Pathway Intermediates, a global animal nutrition leader which has decades of experience in the animal industry.
The two set up a collaboration to develop bacteriophage-based feed additives as antibiotic alternatives, using a bacteriophage cocktail platform and commercialization experiences.
We firmly believe that the future of animal feed additives lies in precision solutions with more target-specific products. Successfully reducing the use of antibiotics would be a step forward for the health and safety of people, animals, and the environment.
[Feedinfo] Tell me about how your bacteriophages are being used. Are these therapeutic or preventative solutions? How often do they need to be fed for optimal effect?
[Dr. Hyunil Kim] Humanity is already facing the alarming occurrence of a variety of antibiotic resistant bacteria. Currently, there are some bacteriophage products for therapeutic use. Due to the fundamental differences between antibiotics and bacteriophages, the preferable application in the animal industry is preventative use. By using bacteriophage solutions, we can decrease disease susceptibility and improve gut microflora, contributing to improved productivity. To ensure this effect, it is recommended to apply bacteriophages throughout sensitive stages of an animal’s life. Naturally, the dosage might depend on the growth phase of the animals, or their environment.
[Feedinfo] Bacteriophages are a targeted solution against specific bacteria. Against what pathogens are ProBe-Bac® SE and ProBe-Bac® PE effective? What conditions do they help to prevent?
[Dr. Hyunil Kim] Salmonella, pathogenic Escherichia coli, and Clostridium perfringens account for approximately 80% of major bacterial diseases, although the exact figure will vary by region. Based on this, ProBe-Bac® is an optimized bacteriophage cocktail product designed to effectively control these pathogenic bacteria. As you pointed out, there are two versions of ProBe-Bac®. ProBe-Bac® SE is a swine-targeted product while ProBe-Bac® PE is used in poultry.
When animals are under stress, the gut microflora shifts negatively resulting in increased disease susceptibility and compromised productivity. By applying ProBe-Bac® to animals, bacteriophages effectively control the growth of pathogenic bacteria and improve gut microflora. Specifically, ProBe-Bac® can help to prevent Salmonellosis, colibacillosis, edema, and necrotic enteritidis in swine, and poultry typhoid, salmonellosis, and avian colibacillosis in poultry.
[Feedinfo] What kinds of trials have been run to demonstrate the products’ effectiveness?
[Kenneth Seo] Pathway Intermediates have conducted many scientific, technical, and commercial trials with ProBe-Bac®. Specifically, we have proved the meaningful effectiveness of bacteriophages against pathogenic bacteria such as Salmonella spp., E. coli spp., and Clostridium spp. in the animal industry, in both in vitro tests and in vivo challenge trials. The in vitro tests were supported by Optipharm and in vivo trials have been conducted in collaboration with universities, leading global integrators, and feed mills in many countries and species.
[Feedinfo] Can you explain the concept of your “real time upgrade system”? How does Pathway Intermediates’ phage solution adapt to changes in the microbial populations that you are monitoring?
[Dr. Hyunil Kim] We aim to develop the best bacteriophage cocktails and improve the phage efficacy. A primary consideration for bacteriophage products is keeping up with the number of diverse bacterial strains and their evolution. We are focused on pathogenic E. coli, Salmonella, and C. perfringens, and in our diagnostic lab, we have been isolating and monitoring the field bacteria for a long time. Based on the accumulated data of more than 200,000 diagnostic cases each year, Optipharm is able to select and provide bacteriophages that best suit the most common diseases, as well as epidemics. As Optipharm operates a monitoring system that verifies the efficacy of bacteriophages against their targeted bacteria, we can check if there are resistant bacteria, or strains against which ProBe-Bac® shows low efficacy. Based on this bacteriophage library, we can easily upgrade or fortify the bacteriophages in ProBe-Bac®. The efficacy of the upgraded product can be seen instantly at farm level. So we call this a “real-time upgrade system”. This is a unique system for bacteriophage products and helps build the credibility of the product.
[Feedinfo] When were ProBe-Bac® PE (for poultry) and ProBe-Bac® SE (for swine) launched? In what markets are they most used today?
[Kenneth Seo] Pathway Intermediates officially launched ProBe-Bac® PE and SE globally in 2020, after more than 5 years of research and development efforts and investment. In terms of the products’ application, we have focused on developing new, practical alternatives for antibiotics in the animal industry. Today, ProBe-Bac® is mainly used in the swine and poultry sectors, and Pathway Intermediates plans to expand ProBe-Bac®’s application into the aqua market in the near future.
[Feedinfo] What are your priorities for the commercial expansion of the ProBe-Bac® line? Where are you focusing your efforts?
[Kenneth Seo] The first step which Pathway Intermediates took is increasing the awareness of this solution in the animal production industry. We stress the importance and scientific validity of bacteriophages and focus on reducing antibiotics in food animal production systems. To support these goals, Pathway Intermediates has been sharing its knowledge of the technology and science of bacteriophages through informative symposia and seminars.
Beyond this, Pathway Intermediates continues to put even more effort into scientific research. At the end of the day, we believe all of our effort will not only increase the understanding of bacteriophages but will also contribute to “clean meat” production.
[Feedinfo] What kinds of market-education work is Pathway Intermediates involved in to help build awareness of this alternative to antibiotics? Why is this an important issue for you?
[Kenneth Seo] We all know that humanity is facing the problem of antibiotic resistance, and it obviously causes negative impacts on human health. However, it is hard to immediately stop using antibiotics because humanity does not have suitable alternatives yet. Still, in the animal industry, bacteriophage technology opens up the possibility of significantly reducing antibiotic use in this sector, even though there are some obstacles that need to be addressed. Pathway Intermediates will overcome these challenges with intense research as well as solid data, improving the understanding of bacteriophages in the animal industry. This will help us move towards a future of antibiotic-free meat production and contribute to human health.
Pathway Intermediates allocated a large budget to further elevate the awareness of bacteriophage and you can look forward to hearing more about this concept in 2023. You will see a lot of activities such as advertisements in global livestock magazines, scientific symposiums and seminars, presentations at open forums, informative movie clips, and content on YouTube, Facebook, and LinkedIn. Pathway Intermediates believes that it has a responsibility to share information on bacteriophages because we are sure that it will change our industry. Indeed, we believe this will elevate the global animal production industry to another level. With ProBe-Bac® and bacteriophage technology, we can achieve non-antibiotic meat or “clean meat” production.
Published in association with Pathway Intermediates