Linking bacterial type I toxins with their actions

Brielle, Régine; Pinel-Marie, Marie-Laure; Felden, Brice

doi:10.1016/j.mib.2016.01.009

Cited by 59 publications

(56 citation statements)

References 53 publications

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“…Type I TA systems have a non-coding RNA antitoxin that complementarily binds to the toxin-encoding mRNA, which results in toxin mRNA degradation or inhibits toxin translation [74,75,76]. Type I toxin and antitoxin genes are independently transcribed from their own promoters, whereas other type TA operons are commonly co-transcribed from a single promoter upstream of the antitoxin gene.…”

Section: Functions Of Six Different Types Of Bacterial Ta Systemsmentioning

confidence: 99%

“…Most of type I toxins are small hydrophobic peptides that disrupt bacterial membrane integrity and thereby cause defects in membrane potential and cell division. They are predicted to have a conserved α-helical transmembrane domain for pore formation, but their cellular functions and action mechanisms are highly diverse [74,75,77]. It remains to be investigated whether the pore formation provokes a detergent-like effect, as is found in many antibacterial peptides [78].…”

Section: Functions Of Six Different Types Of Bacterial Ta Systemsmentioning

confidence: 99%

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Structure, Biology, and Therapeutic Application of Toxin–Antitoxin Systems in Pathogenic Bacteria

Lee

2016

Toxins

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Bacterial toxin–antitoxin (TA) systems have received increasing attention for their diverse identities, structures, and functional implications in cell cycle arrest and survival against environmental stresses such as nutrient deficiency, antibiotic treatments, and immune system attacks. In this review, we describe the biological functions and the auto-regulatory mechanisms of six different types of TA systems, among which the type II TA system has been most extensively studied. The functions of type II toxins include mRNA/tRNA cleavage, gyrase/ribosome poison, and protein phosphorylation, which can be neutralized by their cognate antitoxins. We mainly explore the similar but divergent structures of type II TA proteins from 12 important pathogenic bacteria, including various aspects of protein–protein interactions. Accumulating knowledge about the structure–function correlation of TA systems from pathogenic bacteria has facilitated a novel strategy to develop antibiotic drugs that target specific pathogens. These molecules could increase the intrinsic activity of the toxin by artificially interfering with the intermolecular network of the TA systems.

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Section: Functions Of Six Different Types Of Bacterial Ta Systemsmentioning

confidence: 99%

Section: Functions Of Six Different Types Of Bacterial Ta Systemsmentioning

confidence: 99%

Structure, Biology, and Therapeutic Application of Toxin–Antitoxin Systems in Pathogenic Bacteria

Lee

2016

Toxins

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“…Type III toxins are all nucleases. Type I toxins are predominately predicted membrane disrupting proteins (Table 1) 41 ; though the exact mechanisms of toxicity are not always known, the membrane is not not necessarily a phyla-specific target, as discussed with Fst below.…”

Section: Toxin Target and Regulation Of Toxins As Factors In Ta Familmentioning

confidence: 99%

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

et al. 2017

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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.

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“…This transcriptional organisation favours an excess of antitoxin in homeostatic conditions where the toxin is inhibited. The harmful activities of the toxins are due to their interference with essential cellular processes including DNA replication, translation, cell wall synthesis, and maintenance of membrane integrity [2,3,4,5,6]. …”

Section: Introductionmentioning

confidence: 99%

“…Firstly, translation of the mRNA into the toxic protein is hindered as the antitoxin RNA is usually complementary to the region containing the ribosome binding site (RBS) of the toxin transcript or directly competes with ribosomes. In addition to blocking translation initiation, the antitoxin/toxin RNA duplexes are the targets of cellular RNases and thus antitoxin binding ultimately leads to degradation of the toxin transcripts [6]. Aside from Type I TA systems, inhibition of toxin translation is also used by the only Type V system identified so far [7].…”

Section: Introductionmentioning

confidence: 99%

Structure, Evolution, and Functions of Bacterial Type III Toxin-Antitoxin Systems

Goeders

Chai

Chen

et al. 2016

Toxins

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Toxin-antitoxin (TA) systems are small genetic modules that encode a toxin (that targets an essential cellular process) and an antitoxin that neutralises or suppresses the deleterious effect of the toxin. Based on the molecular nature of the toxin and antitoxin components, TA systems are categorised into different types. Type III TA systems, the focus of this review, are composed of a toxic endoribonuclease neutralised by a non-coding RNA antitoxin in a pseudoknotted configuration. Bioinformatic analysis shows that the Type III systems can be classified into subtypes. These TA systems were originally discovered through a phage resistance phenotype arising due to a process akin to an altruistic suicide; the phenomenon of abortive infection. Some Type III TA systems are bifunctional and can stabilise plasmids during vegetative growth and sporulation. Features particular to Type III systems are explored here, emphasising some of the characteristics of the RNA antitoxin and how these may affect the co-evolutionary relationship between toxins and cognate antitoxins in their quaternary structures. Finally, an updated analysis of the distribution and diversity of these systems are presented and discussed.

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Linking bacterial type I toxins with their actions

Cited by 59 publications

References 53 publications

Structure, Biology, and Therapeutic Application of Toxin–Antitoxin Systems in Pathogenic Bacteria

Structure, Biology, and Therapeutic Application of Toxin–Antitoxin Systems in Pathogenic Bacteria

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

Structure, Evolution, and Functions of Bacterial Type III Toxin-Antitoxin Systems

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