Why so narrow: Distribution of anti-sense regulated, type I toxin-antitoxin systems compared with type II and type III systems

Abstract

Toxin-antitoxin (TA) systems are gene modules that appear to be horizontally mobile across a wide range of prokaryotes. It has been proposed that type I TA systems, with an antisense RNA-antitoxin, are less mobile than other TAs that rely on direct toxin-antitoxin binding but no direct comparisons have been made. We searched for type I, II and III toxin families using iterative searches with profile hidden Markov models across phyla and replicons. The distribution of type I toxin families were comparatively narrow, but these patterns weakened with recently discovered families. We discuss how the function and phenotypes of TA systems as well as biases in our search methods may account for differences in their distribution.

Keywords: Antisense RNA; horizontal gene transfer; post-segregational killing; toxin-antitoxin systems.

Figure 1.

Operon organization and regulation of type I, type II and type III TA systems. Type I TA systems have an antisense RNA antitoxin that binds the toxin mRNA, leading to mRNA degradation. If the antitoxin does not bind, the toxin is translated and is free to target cellular membranes or nucleic acids.⁹ Type II TA systems have a protein antitoxin that directly binds the protein toxin, preventing the toxin from targeting various components of central dogma reactions. The bound toxin and antitoxin interact with their own promoter to control transcription in a process known as conditional cooperativity Type III TA antitoxins are RNA repeats. The cognate toxin is a nuclease that specifically cuts its own RNA repeats before the repeats directly bind and inhibit the toxin. All systems rely on careful titration of toxin and antitoxin in the cell. The antitoxin degrades faster in the cell, and a reduction of transcription and translation rates due to cellular stress or gene loss can free the toxin causing cell death or growth arrest.

Figure 2.

Percent of species within each phyla or replicon that contain a loci from a given type I, type II and type III TA toxin family. HMMs for each TA family were derived from known amino acid sequences and used to search a database of phage, plasmid, and bacterial chromosome sequences subjected to 6-frame translations to derive all possible amino acid sequences from that sequence. This includes short ORFs that are typical of type I toxins. For each phyla or replicon, the percent of total species in the database (left of figure) that contain at least one locus of that toxin is reported (boxes).