Viruses That Attack Bacteria
Proteon Pharmaceuticals, a £ód¼-based company that is conducting advanced research to produce a bacteriophage-based preparation to prevent salmonella infections in farm animals, was named the third most innovative biotechnology company in Central and Eastern Europe at this year’s BioForum fair in £ód¼.
The BioForum fair is the largest trade event for the biotechnology sector in Poland and Central Europe. The organizer is the Bio-Tech Consulting company in £ód¼.
This year’s BioForum, held in May for the ninth time, drew over 1,500 participants from 20 countries, including 100 exhibitors who came to show over 100 research and development projects. The BioPartnering section of the event encompassed over 900 business meetings.
As part of the event the Top CE Biotech Innovative Companies Contest was held to select the most innovative biotechnology company in Central and Eastern Europe. One of the prizes went to Proteon Pharmaceuticals.
Biological weapon
“Bacteriophages were first used as a protective measure against harmful pathogens a century ago, but later the technique was forgotten,” says Jaros³aw Dastych, M.D., owner of Proteon Pharmaceuticals. “The expertise in making practical use of bacteriophages mainly survived in the former Soviet republic of Georgia and in Poland. Now that bacteria are growing increasingly resistant to antibiotics, this biological method to combat bacteria, abandoned in favor of antibiotics, is back in fashion.”
Proteon Pharmaceuticals was established in 2005. At first it focused on carrying out in vitro immunotoxicity tests, with a special focus on Fluorescent Cell Chip (FCC) technology applied to detect the immunomodulating effects of substances that could be used to produce anti-inflammatory, anti-allergic, immunosuppressive and anti-cancer drugs. In October 2009, the company began to deal with bacteriophages, or viruses that attack bacteria.
Bactieriophages are extremely specialized and each strain attacks a different kind of bacteria. Once a phage enters into a bacterial cell, it starts replicating to 30-50 copies, causing the bacterium to disintegrate. Sometimes the viral genes merge with the bacterial genome, reproducing together with the host, first waiting and then destroying it. When a patient is administered a bacteriophage, the virus replicates for only as long as the bacteria of a particular strain remain in the patient’s body.
Bacteriophages are not dangerous to humans, because they never attack human cells. However, in order to multiply a given bacteriophage strain, microbiologists need to culture bacteria that the phage prey on. If the phage is to be subsequently isolated, the bacteria have to be thoroughly removed. A slight risk occurs that the sample can be contaminated with the bacteria and their toxins.
The phage therapy was originally developed a long time ago, but interest in it resurfaced in the 1990s when after decades of extensive use of antibiotics, many new bacterial strains emerged with a growing resistance to antibiotics. Contemporary therapies combining several kinds of antibiotics frequently fail to contain an infection. This is the case with Staphylococcus aureus which does not respond to antibiotics in 40-50 percent of hospital-acquired infections. Meanwhile, an antibiotic-resistant bacterium like this may turn out to be defenseless against bacteriophages.
Researchers in Tbilisi, Georgia, and Wroc³aw, Poland, are looking for new phages, because bacteria develop resistance to their viral enemies as well. The interest in bacteriophages nevertheless continues to grow both in the medical community and beyond. For example, a company in the United States has registered an aerosol spray containing bacteriophages to protect meat in cold stores from a dangerous bacterium called Listeria monocytogenes.
Bacteriophages vs. salmonella
One of the most serious problems in large-scale production of poultry and eggs is Salmonella, a bacterium that occurs naturally in birds. The genus has many subtypes that are difficult to distinguish and birds need some of them to survive—the way humans need the Escherichia coli genus. Problems begin when the bacteria multiply beyond control, causing trouble at poultry farms and posing a threat to consumers.
The EU has developed a program to eliminate Salmonella-related hazards, involving regular inspection of birds, poultry meat, eggs and chicken coops. When a certain strain of Salmonella is found, the entire flock has to be eradicated, which means enormous losses to poultry breeders. Vaccines have been developed, but they are quite expensive, because each bird has to be inoculated individually and that only makes sense in the case of laying hens. Until recently, antibiotics were commonly added to poultry feed, which kept Salmonella in check. With time, however, the additives triggered antibiotic resistance in the bacteria and in people who ate meat containing antibiotics.
“When the EU banned the use of antibiotics as feed additives, I thought of culturing bacteriophages against Salmonella,” says Dastych. “Phages are not antibiotics and they do not stay in the food chain. Consequently, instead of developing a drug to combat a deadly bacterium, I decided we should start from something that worked on chickens. We have been working with a mixture of three phages that we want to put in a feed additive. I believe this method will be much more efficient than, for example, highly acidic feed additives which sterilize chickens’ digestive tracts and result in poor digestion and slow growth of the birds. We could pick a specific phage strain to attack only certain types of Salmonella. We are aiming for a standardized preparation at the molecular level. We have been examining DNA sequences and analyzing the genomes of each bacteriophage to check if it has been classified before. Most of them have not, because there are lots of different bacteriophages. I believe the study and use of bacteriophages marks a new trend in biotechnology and we will live to see other applications of the method, some of them more successful than others.”
Danuta K. Gruszczyńska
Jaros³aw Dastych, aged 51, is a molecular biologist and a graduate of the Faculty of Biology and Earth Sciences at the University of £ód¼. He obtained his doctoral and postdoctoral degrees in medical sciences from the Medical University of £ód¼.
Dastych runs the Proteon Pharmaceuticals company and heads the Cell Immunology Laboratory at the Polish Academy of Sciences’ Institute for Medical Biology in £ód¼. He has made two international patent applications and authored around 30 research publications printed in trade magazines.
Dastych has managed nine research projects financed by the Ministry of Science and Higher Education, the Foundation for Polish Science, and the European Commission.