Nucleotide-binding and oligomerization domain-like receptors (NLRs) are conserved molecular switches that regulate innate immunity across diverse domains of life. While best known for their roles in i...

Abstract. Low-copy-number plasmids often rely on dedicated maintenance mechanisms, such as partitioning systems, to ensure stable inheritance across genera

Abstract. Low-copy-number plasmids often rely on dedicated maintenance mechanisms, such as partitioning systems, to ensure stable inheritance across genera

Bacterial competition drives the evolution of antibacterial mechanisms, yet how new activities arise remains poorly understood. A major route to innovation is the reuse of pre-existing genetic systems, whereby conserved protein modules are repurposed in new biological contexts to generate new capabilities. Here, we show that the ParB-CTPase fold, a conserved nucleotide-binding module best known for its role in chromosome segregation, can be functionally repurposed as an antibacterial toxin. We identify ToxB, a ParB-like domain embedded within the polymorphic toxin region of contact-dependent inhibition systems and show that it functions as a potent antibacterial effector. Structural and biochemical analyses reveal that ToxB retains the core architecture of the ParB-CTPase fold but lacks DNA-binding capability and preferentially binds ATP. This shift in nucleotide specificity underpins a distinct mode of action, in which ATP binding and hydrolysis trigger rapid nucleoid compaction, chromosome segregation defects, oxidative stress, cell chaining, and ultimately cell lysis. ToxB also exhibits toxic activity in plant cells, suggesting that it targets conserved cellular processes. Together, these findings provide direct experimental evidence that the ParB-NTPase fold is biologically versatile and can be repurposed for biological roles fundamentally distinct from its ancestral function in DNA segregation. ### Competing Interest Statement The authors have declared no competing interest. Wellcome Trust, https://ror.org/029chgv08, 221776/Z/2/Z, 227755/Z/23/Z Biotechnology and Biological Sciences Research Council, https://ror.org/00cwqg982, BB/X01097X/1 Diamond Light Source, MX32728

An immunity-like system functions as a lysis control hub to promote gene transfer agent particle release from host bacterial cells, suggesting that bacterial immune systems may be co-opted to promote ...

Do cutting-edge research at the intersection of cryo‑EM, genome-wide profiling, and AI-driven modelling. Work with world‑class cryo-EM/cryo-ET imaging and AI tools to discover how the dangerous bacter...

Low-copy-number plasmids often rely on dedicated maintenance mechanisms, such as partitioning systems, to ensure stable inheritance across generations. These partition systems actively segregate siste...

Nucleotide triphosphate (NTP)-dependent molecular switches regulate essential cellular processes by cycling between active and inactive states thro...

Join us in exploring the hidden functions of ancient immune proteins in bacteria. Bacteria, like plants and animals, have evolved sophisticated systems to detect and respond to threats.

Nucleotide triphosphate (NTP)-dependent molecular switches regulate essential cellular processes by cycling between active and inactive states through nucleotide binding and hydrolysis. These mechanis...

The ATP- and CTP-dependent ParA-ParB-parS segrosome is a macromolecular complex that segregates chromosomes/plasmids in most bacterial species. CTP...

Bacteria have evolved a wide array of immune systems to detect and defend against external threats including mobile genetic elements (MGEs) such as bacteriophages, plasmids, and transposons. MGEs are ...