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

Abstract

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.

Genomic analyses of Neisseria gonorrhoeae reveal an association of the gonococcal genetic island with antimicrobial resistance

“…Many of GGI encoded genes show similarity to those from the Escherichia coli F-plasmid conjugation system and, the order of the genes in the GGI is highly similar to the IncF family of conjugative plasmids, consistent with the GGI being an ancestral chromosomally inserted plasmid 17, 40. In particular, the DNA methylases, ydg (NEIS2288) and ydhA (NEIS2289) can be found which may enable within host competition between plasmids consistent with the low prevalence of isolates here possessing both a plasmid and the GGI 41 (Supplementary Tables 1 and 4). …”

Recovery of Plasmid pEMB1, Whose Toxin-Antitoxin System Stabilizes an Ampicillin Resistance-Conferring β-Lactamase Gene in Escherichia coli, from Natural Environments

“…ParD-ParE toxin-antitoxin systems are commonly found in bacterial plasmids and chromosomes of Gammaproteobacteria and Alphaproteobacteria (53)(54)(55), and plasmids harboring both TA systems and antibiotic resistance genes are widely distributed in enterococci (24,56). However, to the best of our knowledge, pEMB1 is the first plasmid harboring a ParD-ParE TA system and an ampicillin resistance gene identified from human-influenced (wastewater sludge) and pristine (remote mountain soil) environments.…”

Temporal and Spatial Scaling of the Genetic Structure of a Vector-Borne Plant Pathogen

“…It has been shown that, in a homogeneous environment, colicin-producing Escherichia coli genotypes prevent invasion by colicin-sensitive genotypes, and vice-versa (7). Toxin-antitoxin addiction systems have been described in X. fastidiosa (29,30), and their role in the ecology of this bacterium should be considered (15).…”