Automated discovery and phylogenetic analysis of new toxin-antitoxin systems

Julien Guglielmini,Cédric Szpirer,Michel C Milinkovitch

doi:10.1186/1471-2180-8-104

Abstract

BackgroundAlthough often viewed as elements "at the service of" bacteria, plasmids exhibit replication and maintenance mechanisms that make them purely "selfish DNA" candidates. Toxin-antitoxin (TA) systems are a spectacular example of such mechanisms: a gene coding for a cytotoxic stable protein is preceded by a gene coding for an unstable antitoxin. The toxin being more stable than the antitoxin, absence of the operon causes a reduction of the amount of the latter relative to the amount of the former. Thus, a cell exhibiting a TA system on a plasmid is 'condemned' either not to loose it or to die.ResultsDifferent TA systems have been described and classified in several families, according to similarity and functional parameters. However, given the small size and large divergence among TA system sequences, it is likely that many TA systems are not annotated as such in the rapidly accumulating NCBI database. To detect these putative TA systems, we developed an algorithm that searches public databases on the basis of predefined similarity and TA-specific structural constraints. This approach, using a single starting query sequence for each of the ParE, Doc, and VapC families, and two starting sequences for the MazF/CcdB family, identified over 1,500 putative TA systems. These groups of sequences were analyzed phylogenetically for a better classification and understanding of TA systems evolution.ConclusionThe phylogenetic distributions of the newly uncovered TA systems are very different within the investigated families. The resulting phylogenetic trees are available for browsing and searching through a java program available at .

Highlights

Often viewed as elements "at the service of" bacteria, plasmids exhibit replication and maintenance mechanisms that make them purely "selfish DNA" candidates
Because plasmids sometimes bear genes that provide bacteria with functions that can be adaptive in variable environments, they are often viewed as elements "at the service of" a pool of bacteria, allowing the long-term survival of these lines or species
Thought to occur in many Prokaryotic species [8], most TA systems are organized as follows: a gene coding for a cytotoxic and stable protein is preceded by a DNA sequence coding for an unstable antitoxin protein or antisense RNA that can neutralize the toxic protein or its corresponding mRNA, respectively

Summary

Introduction

Often viewed as elements "at the service of" bacteria, plasmids exhibit replication and maintenance mechanisms that make them purely "selfish DNA" candidates. Because plasmids sometimes bear genes that provide bacteria with functions (such as virulence, resistance to drugs, the ability to exploit a specific source of carbon) that can be adaptive in variable environments, they are often viewed as elements "at the service of" a (intra- or inter-specific) pool of bacteria, allowing the long-term survival of these lines or species. Their ability to autonomously replicate makes plasmids possible purely "selfish DNA" candidates. The transcription of the system is auto-regulated by the binding of the antitoxin

Methods

Results

Conclusion