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Alternative for antibiotics

Antibiotic resistance is a growing concern both in health care and in food production. Especially in health care, antibiotic resistant bacterial infections are becoming increasingly problematic. Furthermore, intensive food production is a major user of antibiotics. The world needs new solutions to address the problems that the extensive antibiotic use has caused.

To address the problem, interest towards targeted removal of pathogens by using bacteriophages (phages) as a therapy method has increased. Phages are natural enemies of bacteria and can be found in places where bacteria are found. These viruses of bacteria have been known for a long time. The results of using phages treating infections for both animals and humans have been extremely encouraging. This is especially important, as viruses are ubiquitous in the environment, infect only bacteria and are harmless to humans and other animals.

The main challenge is that some of the phages are notoriously hard to produce. Traditional methods do not succeed to isolate phages from the environment and grow them by using conventional phage production techniques. Therefore, it is not possible to produce some of the bacteria-infecting viruses in large quantities using conventional phage production methods, which are based on liquid cultures. Although other methods can be used, they make the process too time consuming and hard to implement in a large scale. Another common issue with selected phages concerns quantification by titration, since very often the bacterial growth in titration plates is not optimal and the phage enumeration fails, resulting in loss of time and resources.

Our solution

It is known that most infections start from mucosal surfaces and these infections results in mortality and morbidity worldwide, both in humans and in animals. Our scientists have discovered that our solution in phage production is well suited against those bacteria that live on mucosal membranes.

Just as there are many kinds of bacteria, there are several types of bacteriophages. Each kind of phage will only attack a certain bacterium. This means that phages can be used to directly target disease-causing bacteria. As stated before, phages are easy to find as they live among the bacteria. The extraction of a certain phage has proved to be difficult, let alone the production in a large scale. Different phages need different methods for their production, quantification and isolation. Our patent protects the solution for this need.

Our invention covers all relevant steps in setting up a phage therapy product: phage isolation, phage production and phage quantification. It provides modified culture medium for growing bacterial hosts rendering the host cells permissive to phage infection. With our solution, we have improved phage yield up to 1000 or even 100 000-fold higher than the conventional method. This enables cost effective phage production in a large scale.

The researcher have discovered that the invention is suitable for:

1. Pseudomonas aeruginosa is a significant human pathogen. The bacterium has many multiresistant strains, and thus has high clinical relevance. P. aeruginosa is considered as opportunistic pathogen, as the infections are often linked with existing disease conditions. It causes especially devastating lung infections in patients with cystic fibrosis but is associated also with severe burns and infections acquired in hospitals. High age is also a major risk factor for multiresistant P. aeruginosa infections.

P. aeruginosa is one of the most important targets for phage therapy. Our invention significantly improves P. aeruginosa phage production during the first 24h of culture in liquid medium. 1000-fold improvement of phage titer is obtained by addition of mucin in bacterial culture. This allows rapid production of phages for therapy approaches.

2. Streptococcus mutans is commonly found in the oral microbiome, and the bacterium is mainly transmitted vertically from parents to children. It causes dental karies and is thus a significant contributor in tooth decay. In its natural habitat – the mouth – the bacterium is naturally in contact with mucosal surfaces.

Culturing S. mutans with mucin improves phage production by 1000-10 000-fold compared to mucin-free culture during 24h. So far, there are only limited number of phages described against S. mutans. Our invention may have a significant role in improving collection of phage isolates.

3. F. columnare is the etiological agent of columnaris disease, a one of the most significant problems in freshwater aquaculture around the world. It affects the epidermal surface and gills of fish and is usually treated with antibiotics (mainly oxytetracycline). Antibiotics do not eradicate the pathogen from the environment; as an opportunist, it can survive outside the fish host for several months. One of the alternatives for antibiotics in to control disease outbreaks is the use of F. columnare -infecting phages. Our invention gives the opportunity to set up large scale production for aquaculture needs.

WHAT NEXT?

The patent is valid for 20 years. The European patent and the US patent applications for this invention are in pending. Innovation Services is now looking for a partner to commercialize this invention. This means that we are looking for partners and companies to bring our invention to market, where it can help solve the problem of antibiotic-resistant bacterial infections.

At the Ä¢¹½Ö±²¥, inventors receive 50% of the net profit when the research results owned by the university are sold or licensed. The university bears the costs and risks. Innovation services are primarily responsible for the commercialisation and contacting the potential customers of our research results as the researcher(s) continue their research. Naturally, innovation services need the support of inventors because they are experts in the invention.

Invention in brief:

→ Inventors: Lotta-Riina Sundberg, Gabriel Almeida and Elina Laanto from the Department of Biological and Environmental Science

→ Our phage production invention allows rapid production of selected phages for therapy approaches.

→ Ä¢¹½Ö±²¥ is searching a commercial partner to exploit the invention.

→ Patent information:
FI129085B; EP3746550A1; US2021047625A1

If you have think you have made an invention or have research result you think could have commercial value, innovation services are here to help you.

More Information: 

Laura Aineslahti, Innovation Advisor
Riikka Reitzer, Senior IPR-Adviser
Innovation Services