Bacteriophages – often reffered to as simply phages – are viruses that pray on bacteria. Since they are extremely effective at killing their hosts, these viruses are used to treat bacterial infections. Research on bacteriophages is one of the oldest fields in molecular biology. However, when antibiotics were discovered, phage research somewhat fell into oblivion. In recent years, however, the growing need to combat antibiotic resistance has made phage research more relevant than ever.
– Bacteriophages are effective precision tools when you want to combat a specific infection. While antibiotics often wipe out all bacteria, bacteriophages are picky eaters and specialize in a certain type of bacteria. The tricky part is just finding the right phage for the right bacterial pathogen, says Vasili Hauryliuk, senior lecturer in medical biochemistry at Lund University.
But just as bacteria use resistance factors to defeat antibiotics, they also use antiphage defense systems to protect themselves against bacteriophages. The most well-known is the Nobel Prize-winning CRISPR, but there are many more. Together, they constitute the bacterial antiviral immune system.
– To be able to develop new phage therapies, we therefore need to understand how the bacterial immune system works and what countermeasures they take to fight viruses.
One such defenses is the recently discovered TAC (Toxin-Antitoxin-Chaperone) system. An international consortium led by Vasili Hauryliuk and Gemma Atkinson, researchers at Lund University, has now revealed how the system detects phage infection and how the bacteria defeat the invading virus.
– The system consists of three proteins: toxin (T), antitoxin (A), and chaperone (C). The antitoxin is very effective at neutralizing the toxin, but the antitoxin is unstable and breaks down quickly if it is not protected by the chaperone, says Gemma Atkinson.
When the bacterium is attacked by the phage, the chaperone binds to viral protein instead of the antitoxin, which means the antitoxin breaks down and the toxin is released. The bacterium becomes poisoned and cannot produce more phage particles. This stops the spread of the phage infection in the bacterial population. The chaperone is thus a key protein in the bacterium's immune defense when it comes to detecting bacteriophages.
– Both the human immune system and the bacterial immune system are rich sourses of molecular tools. These molecular machines specifically recognize pathogens and act upon detecting the danger – and this is something that can be exploited for biodechnological and biomedical applications. CRISPR and antibody technology are good examples, but there are many more. We now want to continue investigating the TAC system and see how we can reprogram it to recognize specific proteins to ultimately control this bacterial immune system, concludes Vasili Hauryliuk.
