Mechanism of phage sensing and restriction by toxin-antitoxin-chaperone systems

\ua9 2024 The Author(s). Toxin-antitoxins (TAs) are prokaryotic two-gene systems composed of a toxin neutralized by an antitoxin. Toxin-antitoxin-chaperone (TAC) systems additionally include a SecB-like chaperone that stabilizes the antitoxin by recognizing its chaperone addiction (ChAD) element. TACs mediate antiphage defense, but the mechanisms of viral sensing and restriction are unexplored. We identify two Escherichia coli antiphage TAC systems containing host inhibition of growth (HigBA) and CmdTA TA modules, HigBAC and CmdTAC. HigBAC is triggered through recognition of the gpV major tail protein of phage λ. Chaperone HigC recognizes gpV and ChAD via analogous aromatic molecular patterns, with gpV outcompeting ChAD to trigger toxicity. For CmdTAC, the CmdT ADP-ribosyltransferase toxin modifies mRNA to halt protein synthesis and limit phage propagation. Finally, we establish the modularity of TACs by creating a hybrid broad-spectrum antiphage system combining the CmdTA TA warhead with a HigC chaperone phage sensor. Collectively, these findings reveal the potential of TAC systems in broad-spectrum antiphage defense

The Battle for a Sustainable Food Supply

Since the time that Homo sapiens took up farming, a battle has been waged against pests and diseases which can cause significant losses in crop yield and threaten a sustainable food supply. Initially, early control techniques included religious practices or folk magic, hand removal of weeds and insects, and “chemical” techniques such as smokes, easily available minerals, oils and plant extracts known to have pesticidal activity. But it was not until the early twentieth century that real progress was made when a large number of compounds became available for testing as pesticides due to the upsurge in organic chemistry. The period after the 1940s saw the introduction of important families of chemicals, such as the phenoxy acid herbicides, the organochlorine insecticides and the dithiocarbamate fungicides. The introduction of new pesticides led to significant yield increases, but concern arose over their possible negative effects on human health and the environment. In time, resistance started to occur, making these pesticides less effective. This led agrochemical companies putting in place research looking for new modes of action and giving less toxic and more environmentally friendly products. These research programmes gave rise to new pesticide families, such as the sulfonylurea herbicides, the strobilurin fungicides and the neonicotinoid insecticide classes