Investigation of the functional link between abortive infection and toxin-antitoxin systems

Abstract

Bacteria are constantly faced by phage predation and various environmental stresses. In response, bacteria have amassed diverse genetic systems enabling their survival in ecological niches. Abortive infection (Abi) systems are ‘altruistic’ cell death modules activated in a phage-infected bacterium and provide protection to the clonal bacterial population. Previously, our analysis of ToxIN from Pectobacterium atrosepticum provided the first direct link between Abi and toxin-antitoxin (TA) systems and revealed a new type (type III) of TA mechanism. Here, we tested the functional overlaps between TA and Abi systems. We discovered that Lactococcus lactis AbiE system and a homologue situated in a genomic island in Streptococcus agalactiae function as TA systems. These TA systems have non-interacting protein components (i.e. are type IV TA systems) and are found in archaeal and bacterial genomes, plasmids and mobile genetic elements. The antitoxin has a winged-helix-turn-helix domain that binds a conserved inverted repeat and represses the transcription of the TA/Abi operon. Furthermore, the toxin functions through a mechanism not previously identified in TA systems. AbiEii is a nucleotidyltransferase that belongs to the DNA polymerase beta protein superfamily and specifically binds to GTP; however its molecular target remains to be classified. The identification of another Abi as a TA system further strengthens the model that a functional link exists between some Abi and TA systems.