Bacterial type II toxin-antitoxin systems acting through post-translational modifications

Abstract

The post-translational modification (PTM) serves as an important molecular switch mechanism to modulate diverse biological functions in response to specific cues. Though more commonly found in eukaryotic cells, many PTMs have been identified and characterized in bacteria over the past decade, highlighting the importance of PTMs in regulating bacterial physiology. Several bacterial PTM enzymes have been characterized to function as the toxin component of type II TA systems, which consist of a toxin that inhibits cell growth and an antitoxin that protects the cell from poisoning by the toxin. While TA systems can be classified into seven types based on nature of the antitoxin and its activity, type II TA systems are perhaps the most studied among the different TA types and widely distributed in eubacteria and archaea. The type II toxins possessing PTM activities typically modify various cellular targets mostly associated with protein translation and DNA replication. This review mainly focuses on the enzymatic activities, target specificities, antitoxin neutralizing mechanisms of the different families of PTM toxins. We also proposed that TA systems can be conceptually viewed as molecular switches where the ‘on’ and ‘off’ state of the system is tightly controlled by antitoxins and discussed the perspective on toxins having other physiologically roles apart from growth inhibition by acting on the nonessential cellular targets.

The two paralogous copies of the YoeB–YefM toxin–antitoxin module in Staphylococcus aureus differ in DNA binding and recognition patterns

“…TA systems are ubiquitous genetic module found in varieties of bacteria and archea that could participate in various physiological processes, such as phage abortive infections, metabolism, cell growth, and viability during stress conditions ( 29 ). Type II TA systems are the most abundant genetic modules in bacterial species, in which both toxin and antitoxin form tight noncovalent complex.…”

Type II toxin–antitoxin system, RatAB, contributes to oxidative resistance, biofilm formation and virulence of Edwardsiella piscicida

“…N, the number of times the experiment was performed. *p < 0.05; **p < 0.01 Yashiro et al, 2020;Zhang et al, 2020). E. piscicida has gradually become a primary pathogen that threatens global aquaculture, and it has attracted increasing attention.…”

“…Due to the diversity and importance of its role, the type II TA system has become the basis for more research (Dai et al, 2021; Klemenčič et al, 2021; Yashiro et al, 2020; Zhang et al, 2020). E .…”

Disruption of MenT2 toxin impairs the growth of Mycobacterium tuberculosis in guinea pigs

“…The ectopic expression of toxins belonging to TA systems leads to growth inhibition in either a bactericidal or a bacteriostatic manner. Several studies have shown that toxins inhibit important metabolic processes such as translation, cell division, cell wall assembly and DNA replication [1,2,[6][7][8][9]. The antitoxin autoregulates the expression of the TA system and neutralizes the activity of the cognate toxin [1,10,11].…”