MazEF Toxin-Antitoxin System-Mediated DNA Damage Stress Response in Deinococcus radiodurans

Abstract

Deinococcus radiodurans shows marked resistance to various types of DNA-damaging agents, including mitomycin C (MMC). A type II toxin-antitoxin (TA) system that responds to DNA damage stress was identified in D. radiodurans, comprising the toxin MazF-dr and the antitoxin MazE-dr. The cleavage specificity of MazF-dr, an endoribonuclease, was previously characterized. Here, we further investigated the regulatory role of the MazEF system in the response to DNA damage stress in D. radiodurans. The crystal structure of D. radiodurans MazF (MazF-dr) was determined at a resolution of 1.3 Å and is the first structure of the toxin of the TA system of D. radiodurans. MazF-dr forms a dimer mediated by the presence of interlocked loops. Transcriptional analysis revealed 650 downregulated genes in the wild-type (WT) strain, but not in the mazEF mutant strain, which are potentially regulated by MazEF-dr in response to MMC treatment. Some of these genes are involved in membrane trafficking and metal ion transportation. Subsequently, compared with the WT strain, the mazEF mutant strain exhibited much lower MMC-induced intracellular iron concentrations, reactive oxygen species (ROS), and protein carbonylation levels. These results provide evidence that MazEF-mediated cell death in D. radiodurans might be caused by an increase in ROS accumulation upon DNA damage stress.

The novel type II toxin–antitoxin PacTA modulates Pseudomonas aeruginosa iron homeostasis by obstructing the DNA-binding activity of Fur

“…Regulation of iron uptake by type II TA systems such as P. aeruginosa HigBA and Deinococcus radiodurans MazEF have been investigated previously ( 16 , 42 ), however, the regulatory functions in iron uptake have not been reported for GNAT toxins. In P. aeruginosa , the major intracellular iron response regulator is Fur, which is also a conserved global regulator across many bacteria ( 15 ).…”

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

“…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 .…”

“…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 F I G U R E 6 Effects of ratA and ratAB mutations on survival and replication in phagocytes. RAW264.7 cells were incubated with TX01ΔratA, TX01ΔratAB, TX01ΔratAC, TX01ΔratABC and TX01 for 2 h; then, extracellular bacteria were killed.…”

Functional Characterization of the mazEF Toxin-Antitoxin System in the Pathogenic Bacterium Agrobacterium tumefaciens

“…The Kis-Kid in plasmid R1 is known to encode the addiction modules to prevent the loss of plasmids through a mechanism known as post-segregational killing [7,25,26]. Recently, a MazEF homolog (MazF-dr) in Deinococcus radiodurans responds by an increase in ROS accumulation upon DNA damage stress [27]. Moreover, MazF in Staphylococcus aureus may contribute to reversible bacteria dormancy through activation of translation rescue, ribosome hibernation, the increase of cell wall thickness, and the decrease of cell division [28].…”