The Importance of the Expendable: Toxin–Antitoxin Genes in Plasmids and Chromosomes

Abstract

Toxin–antitoxin (TA) genes were first reported in plasmids and were considered expendable genetic cassettes involved in the stable maintenance of the plasmid replicon by interfering with growth and/or viability of bacteria in which the plasmid was lost. TAs were later found in bacterial chromosomes and also in integrated mobile genetic elements; they were proposed to be involved in the bacterial response to stressful situations. At present, 100s of TAs have been identified and classified in up to six families (I to VI), with those belonging to the type II (constituted by two protein components) being the most studied. Based on well-characterized examples of several type II TAs, we discuss in this review that irrespective of their locations in plasmids or chromosomes, TAs functionally overlap as indicated by: (i) in both locations they can mediate the maintenance of genetic elements to which they are physical linked, and (ii) they can induce persistence or virulence in response to stress situations. Examples of functional confluences in homologous TA systems with different locations are also given. We also consider whether the physiological role of TAs is due to their genetic organization as operons or to their inherent properties, like the short lifespan of the antitoxin component.

Integrity and stability of virulence plasmids fromPseudomonas syringaeare modulated by mobile genetic elements and multiple toxin-antitoxin systems

“…Here we show that TA systems are frequently found in plasmids of P. syringae and that they significantly contribute to the maintenance of virulence genes. TA systems have been involved in a disparity of functions including, among others, the stabilization of plasmids and other mobile genetic elements, biofilm formation, modulation of bacterial persistence, resistance to antibacterial compounds, and prevention of large scale deletions in the chromosome, plasmids and episomes [51,52,61,62]. Our results show that genes found in plasmids of the plant pathogen P. syringae can be eliminated with high frequency because of plasmid loss and rearrangements mediated by mobile genetic elements.…”

Megaplasmids on the Rise: Combining Sequencing Approaches to Fully Resolve a Carbapenemase-Encoding Plasmid in a Proposed NovelPseudomonasSpecies

“…NCBI’s CDD calls 42.1% (256) of the predicted CDS for pJBCL41 ( Table S1 ), indicating that most genes encode proteins of unknown function. The backbone of this megaplasmid harbours genes predicted to be responsible for plasmid replication, heavy metal resistance and carries two predicted type-II toxin-antitoxin (TA) systems and genes encoding for partition systems ( Figure 1 ) [43]. Several genes encoding transport and metabolic processes, as well as transposable elements and CDS associated with transcription, regulatory, chemotaxis signal transduction and mobility functions could be identified.…”

“…The replication module defines plasmid copy number and plasmid survival in several hosts. Low copy-number plasmids are more frequently lost, due to random assortment at cell division [2, 3] and extra stability modules, such as TA and partition systems, may be required to ensure that large plasmids such as pJBCL41 are maintained [43, 59].…”

Antisense and yet sensitive: Copy number control of rolling circle‐replicating plasmids by small RNAs

“…the single-stranded origin of replication, sso (filled circle in blue), is generated in the ssDNA intermediate by intrastrand pairing. More detailed representations of the mechanism of replication by the RC-mode have been published (Espinosa, 2013;Khan, 2005;Lorenzo-Díaz, Fernández-López, Garcillán-Barcia, & Espinosa, 2014;Ruiz-Masó et al, 2015) 3 | CONTROL AND DISTRIBUTION OF PLASMID COPY NUMBERS Stable plasmid inheritance can be achieved by several means such as, at least: (a) integration into the host chromosome so that the plasmid copy number is identical to that of the chromosome (Dempsey & Dubnau, 1989); (b) incorporating into the plasmid backbone some genes that participate in plasmid stable inheritance, like those belonging to the toxin-antitoxin categories (Díaz-Orejas, Espinosa, & Yeo, 2017), (c) incorporating partitioning systems (Austin & Nordström, 1990;Funnell, 2016;Oliva, 2016), and (d) reducing their size and increasing their number of copies so that the probability of plasmid loss is reduced . RCR-plasmids are included in the latter case.…”