Evaluating the Potential for Cross-Interactions of Antitoxins in Type II TA Systems

Abstract

The diversity of Type-II toxin–antitoxin (TA) systems in bacterial genomes requires tightly controlled interaction specificity to ensure protection of the cell, and potentially to limit cross-talk between toxin–antitoxin pairs of the same family of TA systems. Further, there is a redundant use of toxin folds for different cellular targets and complexation with different classes of antitoxins, increasing the apparent requirement for the insulation of interactions. The presence of Type II TA systems has remained enigmatic with respect to potential benefits imparted to the host cells. In some cases, they play clear roles in survival associated with unfavorable growth conditions. More generally, they can also serve as a “cure” against acquisition of highly similar TA systems such as those found on plasmids or invading genetic elements that frequently carry virulence and resistance genes. The latter model is predicated on the ability of these highly specific cognate antitoxin–toxin interactions to form cross-reactions between chromosomal antitoxins and invading toxins. This review summarizes advances in the Type II TA system models with an emphasis on antitoxin cross-reactivity, including with invading genetic elements and cases where toxin proteins share a common fold yet interact with different families of antitoxins.

PrrT/A, a Pseudomonas aeruginosa Bacterial Encoded Toxin-Antitoxin System Involved in Prophage Regulation and Biofilm Formation

“…In contrast, it was shown that the higA mutant exhibits reversed phenotype with decreased biofilm formation, elevation in PDEs expression, and reduced c-di-GMP levels ( 22 , 41 ). The contrasting results are probably attributable to the fact that prrT/A is a combined system in which the antitoxin mutant effect is mainly due to the upregulation of the toxin, as the ParE toxin was shown to enhance biofilm formation in E. coli ( 37 ) significantly.…”

“…It can only occur if some cross-regulation between other chromosomal TA systems has occurred. An interaction between noncognate complexes of toxins and antitoxins, which can bind to other TA promoter regions and regulate the expression, has been reported ( 36 – 38 ).…”

“…TA systems can compensate for each other by cross-reactivity. Therefore, single toxins or antitoxins can still influence the bacteria by reacting with other chromosomal or plasmid-encoded antitoxins or toxins ( 36 , 37 ). Considering this cross-reactivity ability of TA systems, a reasonable assumption would be some toxin downregulation in the prrA OE strain due to an interaction with either a bacterial (PA14) or phage-encoded toxin.…”

Toxin–Antitoxin Systems in Pathogenic Bacteria

“…This work contributes to the understanding of TA interfaces and it offers a structure-based explanation for non-cognate toxin-antitoxin interactions [8]. Tu et al revised the concept that a toxin paralogue may provide a "cure" against the acquisition of highly similar TA systems, such as those found on plasmids or invading genetic elements that frequently carry virulence and resistance genes [9]. Only limited cross-reactions have been observed between chromosomal and mobile genetic elements systems, perhaps due to bias in the type of experiments and functions of TA systems pursued.…”

Análise do sistema toxina-antitoxina HipA/B na indução da persistência bacteriana de cepas de >i<Escherichia coli>/i< extraintestinal

“…No primeiro grupo a antitoxina é uma RNAse que degrada o mRNA da toxina. O sistema GhoS-GhoT é um representante do grupo V (WEN;BEHIELS;DEVREESE, 2014;MASUDA et al, 2012;WANG et al, 2012) presentes em cromossomos e 13 presentes em plasmídeos (TU et al, 2020).…”