Jan-Willem Veening

@veeninglab.com

Professor and director at the Department of Fundamental Microbiology, University of Lausanne, https://veeninglab.com/. Interested in antibiotic resistance, bacterial cell biology, host-microbe interactions.

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Latest from the lab and a fantastic collaboration with Eric Brown's team at @mcmasteriidr.bsky.social. Screening for new antibiotics from actinomycete extracts under nutrient-deprived conditions identifies a megacluster of synergistic antibiotics that target biotin biosynthesis. rdcu.be/fqejG

A Streptomyces megacluster encodes synergistic biotin-targeting antibiotics

Nature - In Streptomyces spp., a conserved biosynthetic gene megacluster produces an arsenal of distinct antimicrobials that converge on bacterial biotin biosynthesis as a naturally evolved...

rdcu.be

Another chapter of my thesis is out! We asked whether we could pair proteome-wide AlphaFold screening with Tn-seq to identify biologically relevant protein-protein interactions. We identify ClcR (formerly YerH) as a component of the Rod complex in Gram-positive bacteria. www.pnas.org/doi/10.1073/...

A broadly conserved gram-positive lipoprotein regulates cell elongation | PNAS

The cell wall peptidoglycan (PG) protects virtually all bacteria from osmotic lysis and specifies cell shape. Synthesis of this exoskeleton is carr...

pnas.org

Happy to share the last publication of @bobytaillefer.bsky.social, showing that #T6SS heterogeneity is an attenuation strategy to optimizes the trade-off between competitive killing and survival.

PLOS Biology@plosbiology.org · 2mo ago

The T6SS is a widespread nanoweapon deployed by #bacteria, but why is it deployed heterogeneously? @cascaleslab.bsky.social &co show that #Ecoli adopt distinct #T6SS attacker "ON" & defender "OFF" roles to optimize survival, a key strategy in microbial warfare @plosbiology.org 🧪 plos.io/3S5dL45

Top: Representative confocal fields of the 3 types of TssC-GFP-TssK microcolonies (homogeneous ON, heterogeneous, homogeneous OFF). Scale bars, 10 μm. Bottom:  Model for the role of T6SS phenotypic heterogeneity in EAEC. Top: The Psci1 promoter integrates Fur- and Dam-dependent regulation, generating ON (T6SS⁺, yellow) and OFF (T6SS⁻, blue) subpopulations at a reversible equilibrium. Bottom left: OFF (blue) cells, which do not express T6SS, do not kill competitors but avoid triggering such defences (1). Due to the absence of killing activity, OFF cells are unable to colonize the niche (2). Bottom centre: While ON (yellow) cells assemble and deploy functional T6SS (1) and kill susceptible competitors (2), they provoke retaliatory attacks from defensive T6SS⁺ species (gray) and are eliminated and fail to colonize the niche (3). Bottom right: Heterogeneous ON/OFF population (1) optimizes colonization by killing neighboring cells (2). While ON (yellow) cells are eliminated by counterattacks by defensive T6SS+ species (gray), OFF (blue) cells resist (3) and can ensure a continuous supply of ON cells (4-5) while limiting population-wide exposure to retaliation.

@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...

Repurposing a chromosome segregation ParB-CTPase fold into an ATPase toxin for contact-dependent growth inhibition in plant and animal pathogens

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

biorxiv.org

NEWS: The ERC Scientific Council has listened to the concerns from members of the research community about changes to the re-submission rules, intended to manage the surge in demand for grants. The Scientific Council will readjust some of the changes: link.europa.eu/TBqRQJ

ERC Scientific Council readjusts rules for reapplication

The ERC Scientific Council has listened to the concerns from members of the research community about the recent announcement on changes to the re-submission rules. The changes, intended to manage the ...

link.europa.eu