Amazing stuff! Apparently a suicidal, late stage, last resort defense system.
"... Phages and bacteria are engaged in a constant battle, the virus attempting to circumvent the bacteria’s defenses, and the bacteria racing to find new ways to protect itself. ...
This defense system detects phage infection at a stage when the viral phage has already commandeered the host’s machinery for its own purposes. In the face of annihilation, the ill-fated bacterium activates a defense system that will halt translation, preventing the creation of new proteins and aborting the infection — but dooming itself in the process. ...
has characterized an anti-phage defense system in bacteria, CmdTAC. CmdTAC prevents viral infection by altering the single-stranded genetic code used to produce proteins, messenger RNA.
CmdTAC is a subset of a widespread anti-phage defense mechanism called a toxin-antitoxin system. A TA system is just that: a toxin capable of killing or altering the cell’s processes rendered inert by an associated antitoxin. ...
The uncoupling of CmdC exposes the neutralizing antitoxin CmdA to be degraded, which releases the toxin CmdT to do its lethal work. ..."
CmdTAC is a TA system with an additional element, and the three components generally exist in a stable complex: the toxic CmdT, the antitoxin CmdA, and an additional component called a chaperone, CmdC.
If the phage’s protective capsid protein is present, CmdC disassociates from CmdT and CmdA and interacts with the phage capsid protein instead. In the model outlined in the paper, the chaperone CmdC is, therefore, the sensor of the system, responsible for recognizing when an infection is occurring. ...
From the abstract:
"Host–pathogen conflicts are crucibles of molecular innovation. Selection for immunity to pathogens has driven the evolution of sophisticated immunity mechanisms throughout biology, including in bacterial defence against bacteriophages. Here we characterize the widely distributed anti-phage defence system CmdTAC, which provides robust defence against infection by the T-even family of phages. Our results support a model in which CmdC detects infection by sensing viral capsid proteins, ultimately leading to the activation of a toxic ADP-ribosyltransferase effector protein, CmdT. We show that newly synthesized capsid protein triggers dissociation of the chaperone CmdC from the CmdTAC complex, leading to destabilization and degradation of the antitoxin CmdA, with consequent liberation of the CmdT ADP-ribosyltransferase. Notably, CmdT does not target a protein, DNA or structured RNA, the known targets of other ADP-ribosyltransferases. Instead, CmdT modifies the N6 position of adenine in GA dinucleotides within single-stranded RNAs, leading to arrest of mRNA translation and inhibition of viral replication. Our work reveals a novel mechanism of anti-viral defence and a previously unknown but broadly distributed class of ADP-ribosyltransferases that target mRNA."
A proposed model for CmdTAC contains three elements: the toxic CmdT (red), the antitoxin CmdA (blue), and a chaperone, CmdC (green). During infection, CmdC uncouples from CmdT and CmdA, exposing the neutralizing antitoxin CmdA to be degraded, which releases the toxin CmdT to do its lethal work.
Fig. 5: Model for anti-phage defence by the CmdTAC system.
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