Precise regulation of gene expression ensures gene products are produced at the right time and in the right amounts. Recent works uncovered a new mechanism of bacterial gene regulation based on a clamp sliding and locking in a multi-drug resistance plasmid, RK2. KorB functions as a CTP-dependent DNA-sliding clamp capable of traveling over a long genomic distance. Sliding KorB is captured and locked in place by a partner protein, KorA, forming a stable complex at target promoters to repress transcription. Here, we show that another RK2 regulator, TrbA, also uses this clamp sliding-locking mechanism, and identify an aromatic interface enabling TrbA-KorB-mediated transcriptional repression. Our findings show how a single sliding clamp integrates multiple partners to build a complex transcriptional regulatory network.

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

Structural and single-molecule analyses show the CTPase, KorB, is a sliding DNA clamp that interacts with a clamp-locking protein KorA to inhibit gene expression over distances of more than 1 kb in th...

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

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...

Streptomyces bacteria are the primary source of clinically useful antibiotics. While many two-component systems have been linked to antibiotic biosynthesis in Streptomyces species, few have been well ...

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...

By developing a strategy of metagenomic coassembly and prioritizing divergent marker gene sequences, Bin Chicken efficiently recovers more than 77,000 microbial genomes with high novel diversity, ther...

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

Klebsiella host strains infected with telomere phages can grow to be the dominant lineage in mixed populations.

Abstract. Plasmids promote adaptation of bacteria by facilitating horizontal transfer of diverse genes, notably those conferring antibiotic resistance. Som

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Translocating unfolded polypeptides across membranes is essential in all domains of life and in bacteria requires the conserved Sec machinery and ATP. Bacterial Sec substrates fold outside the cell an...

Streptomyces bacteria make diverse specialised metabolites that form the basis of ~55% of clinically used antibiotics. Despite this, only 3% of their encoded specialised metabolites have been matched ...

Long-distance gene regulation is uncommon in bacteria, and its molecular mechanisms are unclear. Using a combination of structural, biochemical and single-molecule techniques, researchers revealed tha...

Structural and single-molecule analyses show the CTPase, KorB, is a sliding DNA clamp that interacts with a clamp-locking protein KorA to inhibit gene expression over distances of more than 1 kb in th...

Structural and single-molecule analyses show the CTPase, KorB, is a sliding DNA clamp that interacts with a clamp-locking protein KorA to inhibit gene expression over distances of more than 1 kb in th...

Post-doctoral scientists are effective mentors for graduate students. This Perspective discusses how failures to properly credit them for this role has negative consequence for everyone and suggests p...

Throughout the golden age of antibiotic discovery, Streptomyces have been unsurpassed for their ability to produce bioactive metabolites. Yet, this su…

Author summary The precise distribution of genetic material to the progeny is essential for all living organisms, and the ParABS system is critical for this process in most bacteria. Our study provide...

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