@biorxiv-microbiol.bsky.social
Who knew ParB-CTPase fold can kill!!!
A protein fold best known for segregating chromosomes…can be transformed into a potent antibacterial toxin in some plant and animal pathogens.
www.biorxiv.org/content/10.6...
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
Reposting! We’re going to do some amazing science and have a lot of fun doing it!
Sometimes ago Tom @tommclean.bsky.social uncovered a mechanism of bacterial gene regulation based on a clamp sliding and locking in a multi-drug resistance plasmid, RK2.
www.nature.com/articles/s41...
Tung Le
This year Hartland Oration was delivered by Thomas McLean from @wehi-research.bsky.social, a great talk on how does the structure of DNA sliding clamp enable gene silencing on a multidrug-resistance plasmid. 👏 #lorneiandi
Happy International Women’s Day!
We’re celebrating the talented women across WEHI — scientists, students and professional staff — whose passion and expertise help power discoveries that change lives. 🧪
📸 L-R: Jill Chmielewski, Research Officer and Frankie Lyons, PhD student
Here, @tommclean.bsky.social shows that another RK2 regulator, TrbA, likely also use this “clamp sliding-locking” mechanism to regulate gene expression. Interesting how a single sliding clamp might integrate multiple partners to potentially build a complex regulatory network...
shorturl.at/YQJOI
KorB functions as a CTP-dependent DNA-sliding clamp traveling a long genomic distance. Sliding KorB is captured and locked in place by a partner protein, KorA, forming a stable A-B complex at target promoters to repress transcription.
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...
www.nature.com
Come do a PhD with me and @trevor-lithgow.bsky.social at @monashuniversity.bsky.social ! We’re at the leading edge of pathogen biology using cutting edge Cryo-EM and AI-driven genetic screens to uncover the mysteries of outer membrane biology. Reach out to me for a chat!
macsys.org/phd-scholars...
Excited to share this is now published in @narjournal.bsky.social 🎉 see the preprint thread below for a summary of our findings on plasmids with multiple partition systems using the Streptomyces plasmid SCP1 as a model! academic.oup.com/nar/article/...
My second postdoc paper in @tunglejic.bsky.social lab and two of my favorite things in the lab combined: ParB and killing bacteria. Thanks to everyone who helped make this project possible!
Video
Tung Le
shorturl.at
Tom McLean
Victorian Infection and Immunity Network
WEHI (The Walter and Eliza Hall Institute of Medical Research)
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...
Abstract. Low-copy-number plasmids often rely on dedicated maintenance mechanisms, such as partitioning systems, to ensure stable inheritance across genera
Come do a PhD with me and @trevor-lithgow.bsky.social at @monashuniversity.bsky.social ! We’re at the leading edge of pathogen biology using cutting edge Cryo-EM and AI-driven genetic screens to uncover the mysteries of outer membrane biology. Reach out to me for a chat!
macsys.org/phd-scholars...
Leah McPhillips
Jovana Kaljević ⬜️
@biorxiv-microbiol.bsky.social
Who knew ParB-CTPase fold can kill!!!
A protein fold best known for segregating chromosomes…can be transformed into a potent antibacterial toxin in some plant and animal pathogens.
www.biorxiv.org/content/10.6...
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, MX32728www.biorxiv.org
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...
📄 Delighted to share that the preprint of my main PhD work is out now!
👏 A huge thank you to everyone involved, @tommclean.bsky.social, Govind Chandra, Ngat Tran (both not on BlueSky) and especially my PhD supervisor @tunglejic.bsky.social 👏
🧵 below!
www.biorxiv.org/content/10.6...
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...
