Discovering and exploiting the molecular basis of microbial warfare

Bacteria have evolved many ingenious defences against attack by viruses (phages).

Probably the most well-known mechanisms involve degradation of phage nucleic acids to protect the host cell (CRISPR-Cas and restriction-modification systems).

Another widespread defence strategy is so-called abortive infection, where the bacterium altruistically poisons itself with toxins to stop the phage infection in its tracks and prevent its spread to the wider bacterial population. Abortive infection strategies include the toxin-antitoxin systems that we work on in the Atkinson lab.

Recently, we realised that many toxin-antitoxin systems are evolutionary related to other intriguing microbial systems that are potentially also involved in phage defence.

Toxin-mediated defence is a problem for the future success of phage therapy for treating antibiotic-resistant infections.

Thus, the purpose of the project is to understand the ‘hows’ and ‘whys’ of toxin-mediated self-poisoning behaviour in bacteria.

Our aims are to develop computational methods for discovering novel toxin-containing defence systems, to understand the structural and mechanistic basis of toxicity, neutralisation and triggering, to validate predictions through microbiology and biochemistry, to uncover the role of the identified systems in bacterial defence against bacteriophages, and, finally, to engineer phages as more potent therapeutics against antibiotic-resistant pathogens.