Characterisation of Type II toxins discovered through iterative guilt-by-association search

Abstract

The classical toxin-antitoxin (TA) system is encoded as a bicistronic operon consisting of toxin and antitoxin genes. Toxin-antitoxin systems have been studied for more than 30 years and have been shown to play an important role in bacterial immunity and stress response. The most common and best-studied class of TA systems is type II, where both the toxin and the antitoxin are proteins, and the toxin is neutralized by the antitoxin via direct interaction. My thesis helps to uncover the molecular mechanisms of type II toxins found by the bioinformatics tool NetFlax (standing for Network of Flanking genes for toxins and antitoxins) via metabolic labelling assays. I characterize several toxins from different functional domains and show how the toxins affect the bacterial cell using Escherichia coli as the model organism.