Congratulations to Dr Peter Fineran, Raymond Staals (Post-doctoral Fellow) and Hannah Hampton (PhD student) who have been awarded $15,500 from the University of Otago's Dean’s Bequest Funds for their research project entitled Mode of action of a widespread toxin-antitoxin bacteriophage resistance system.
We are surrounded and massively outnumbered by bacteria. Most bacteria are highly beneficial and essential to the environment, ecosystem functions and thus human existence. Even more abundant are bacteriophages, which are viruses that specifically infect bacteria. For example, an estimated 1025 bacteriophage infections occur every second, affecting global nutrient cycles. Bacteria have evolved mechanisms to thwart these invaders, which includes ‘innate immune systems’, such as abortive infection / toxin-antitoxin systems. Following bacteriophage infection, abortive infection and toxin-antitoxin systems elicit a ‘programmed cell death’ that impedes bacteriophage replication and provides population protection by limiting bacteriophage spread. There are currently >20 known abortive infection systems and, with the exception of a few, the molecular basis for bacteriophage resistance is unclear.
We have discovered a two-protein system from Lactococcus lactis, Streptococcus agalactiae and Mycobacterium tuberculosis, which functions via a toxin-antitoxin mechanism. These systems are widespread, found in thousands of sequenced bacterial strains, yet how they work is unknown. In these toxin-antitoxin systems, one protein is toxic to the cell while the other protein protects the cell from this toxicity. Interestingly, the toxin possesses a biochemical activity not previously characterised. We will use a variety of complementary techniques to determine the mode of action and cellular target of this widespread family of toxins in order to understand how they can elicit cell suicide and hence provide bacteriophage resistance.