Durham University

Department of Biosciences

Academic Staff

Dr Tim R Blower, MA (Cantab) MSci PhD

Assistant Professor in the Department of Biosciences
Visiting Assistant Professor in the Department of Chemistry

(email at timothy.blower@durham.ac.uk)

Toxin-antitoxin systems and bacteriophage resistance

Whilst bacteria are often thought of as selfish cells out for their own purposes, increasingly, we can observe that they exist as diverse interacting communities. This is reflected in the ubiquitous presence and implementation of "toxin-antitoxin" systems throughout known Bacterial and Archaeal species. Toxin-antitoxin systems are characterised as small genetic loci encoding two parts. The toxin, when free to act, will target the host cell and stall growth, sometimes to the point of cell death. In the presence of the antitoxin, this effect is negated and cells grow freely.

It might appear peculiar that bacterial cells carry toxin-antitoxin systems, until you consider the potential advantages. For instance, if there aren't enough nutrients to go around, one cell activates its internal toxins, allowing it to grow slower or die, so that the population of clonal bacteria around it can survive. Another example would be when a bacterial cell becomes infected by a bacteria-specific virus, called a bacteriophage. Unchecked, the bacteriophage would replicate, burst out, and infect neighbour cells. If the infected cell shuts down quickly, it can stop viral spread. An example of this type of viral defence is the ToxIN toxin-antitoxin system (Figure 1), which is made up of antitoxic RNA (ToxI) bound to a toxic protein (ToxN).

Figure 1. ToxIN toxin-antitoxin and phage resistance system. ToxI RNA (blue), folds into a pseudoknot that binds and inhibits ToxN protein (pink). Bacteriophage infection reduces the levels of ToxI RNA and releases ToxN to kill the host cell. This atomic resolution structure was obtained by X-ray crystallography (see Blower et al. (2011) Nature Structure and Molecular Biology below).

Harnessing molecular tools from bacteriophage-host interactions

Toxin-antitoxin systems are diverse, with a wide range of roles and many targets, which include the ribosome, DNA replication (via topoisomerases) and the cell wall. This list matches the targets of common antibiotics. By understanding how these toxins inhibit bacterial cell growth, we may be able to co-opt this ability to control bacterial species. This is becoming increasingly important in the face of widespread antibiotic resistance.

Furthermore, as the natural predators of bacteria, it is essential to investigate bacteriophage biology and host-interactions, in particular, the many ways bacteriophages can adapt to avoid host bacteriophage-resistance mechanisms.

A range of molecular biology and biochemical techniques are employed in the lab, including protein biochemistry, genomics and structural analysis through X-ray crystallography.

Research Groups

Department of Biosciences

Wolfson Research Institute for Health and Wellbeing

Indicators of Esteem

Publications

Journal Article