Within-host competition selects for plasmid-encoded toxin–antitoxin systems

Toxin–antitoxin (TA) systems are commonly found on bacterial plasmids. The antitoxin inhibits toxin activity unless the system is lost from the cell. Then the shorter lived antitoxin degrades and the cell becomes susceptible to the toxin. Selection for plasmid-encoded TA systems was initially thought to result from their reducing the number of plasmid-free cells arising during growth in monoculture. However, modelling and experiments have shown that this mechanism can only explain the success of plasmid TA systems under a restricted set of conditions. Previously, we have proposed and tested an alternative model explaining the success of plasmid TA systems as a consequence of competition occurring between plasmids during co-infection of bacterial hosts. Here, we test a further prediction of this model, that competition between plasmids will lead to the biased accumulation of TA systems on plasmids relative to chromosomes. Transposon-encoded TA systems were added to populations of plasmid-containing cells, such that TA systems could insert into either plasmids or chromosomes. These populations were enriched for transposon-containing cells and then incubated in environments that did, or did not, allow effective within-host plasmid competition to occur. Changes in the ratio of plasmid- to chromosome-encoded TA systems were monitored. In agreement with our model, we found that plasmid-encoded TA systems had a competitive advantage, but only when host cells were sensitive to the effect of TA systems. This result demonstrates that within-host competition between plasmids can select for TA systems.     

The solution structure of ParD, the antidote of the ParDE toxin antitoxin module, provides the structural basis for DNA and toxin binding

ParD is the antidote of the plasmid-encoded toxin-antitoxin (TA) system ParD-ParE. These modules rely on differential stabilities of a highly expressed but labile antidote and a stable toxin expressed from one operon. Consequently, loss of the coding plasmid results in loss of the protective antidote and poisoning of the cell. The antidote protein usually also exhibits an autoregulatory function of the operon. In this paper, we present the solution structure of ParD. The repressor activity of ParD is mediated by the N-terminal half of the protein, which adopts a ribbon-helix-helix (RHH) fold. The C-terminal half of the protein is unstructured in the absence of its cognate binding partner ParE. Based on homology with other RHH proteins, we present a model of the ParD-DNA interaction, with the antiparallel beta-strand being inserted into the major groove of DNA. The fusion of the N-terminal DNA-binding RHH motif to the toxin-binding unstructured C-terminal domain is discussed in its evolutionary context.