Figure 9.

Schematic antibacterial strategies using TA systems. (A) Disruptors of TA complex. Direct activation of the toxin is achieved by disruption of the preformed TA complex or prevention of complex formation. The latter can be achieved by either an antitoxin binder or a toxin binder. (B) Activation of cellular proteases. A molecule activates cellular proteases, which promotes the degradation of the labile antitoxin protein from the TA complex. (C) Inhibition of TA gene transcription. A molecule binds to the promoter of TA operon, inhibiting its transcription. The antitoxin is not replenished, and the remaining antitoxin is degraded. Free toxin acts on cellular targets. (D) Inhibition of antitoxin translation. Antisense RNA forms complementary base-paring with antitoxin mRNA, which inhibits antitoxin translation. Free toxin inactivates cellular targets. (E) Bacteriophage infection. Recombinant toxin RNA or DNA enter pathogens via bacteriophage infection. The nucleic acids integrate into the bacterial genome in a lysogenic cycle. The recombinant toxins are produced and cause cell death.