Jack Bravo

Phages with a broad host range are common across ecosystems - Nature Microbiology Proximity-ligation-based sequencing from 111 samples and 5 environments reveals that a substantial proportion of phages infect multiple species.

A fresh view on phage specificity, which challenges the traditional view of a narrow host spectrum of phages by unveiling that multihost associations are common across ecosystems kudos at @mmarbout.bsky.social &
@rkoszul.bsky.social www.nature.com/articles/s41...

Functional RNA splitting drove the evolutionary emergence of type V CRISPR-Cas systems from transposons Transposon-encoded TnpB nucleases gave rise to type V CRISPR-Cas12 effectors through multiple independent domestication events. These systems use diff…

Functional RNA splitting drove the evolutionary emergence of type V CRISPR-Cas systems from transposons - ScienceDirect https://www.sciencedirect.com/science/article/pii/S0092867425010359?dgcid=rss_sd_all

Megaplasmids associate with Escherichia coli and other Enterobacteriaceae Humans and animals are ubiquitously colonized by Enterobacteriaceae , a bacterial family that contains both commensals and clinically significant pathogens. Here, we report Enterobacteriaceae megaplasmids of up to 1.58 Mbp in length in infant and adult guts, and other microbiomes. Of the 19 complete plasmid genomes, one was reconstructed from an Escherichia coli isolate; others were linked to species of Citrobacter and Enterobacter via analysis of genome modification patterns. The detection of related plasmids in different Enterobacteriaceae , conjugation machinery, and more diverse modified motifs in certain plasmids compared to hosts suggests that these elements are self-transmissible, with a broad host range. The plasmids encode multi-drug efflux systems and potential secreted effectors. Up to 208 tRNAs are encoded, and include sequence variants that may counter tRNA-centric defense mechanisms. Overall, the vast megaplasmid coding capacity may broaden host range, increase competitiveness, control invasion by other elements, and counter programmed cell death. ### Competing Interest Statement The authors have declared no competing interest. National Institutes of Health, https://ror.org/01cwqze88, 5R01AI092531 Swiss National Science Foundation, IZJFZ3-177614 Biotechnology and Biological Sciences Research Council, https://ror.org/00cwqg982, BB/X011011/1, BBS/E/QU/230002A, BB/T008717/1 Chan Zuckerberg Initiative (United States), https://ror.org/02qenvm24 Finnish Multidisciplinary Centre of Excellence in Antimicrobial Resistance Research, 346127

Megaplasmids associate with Escherichia coli and other Enterobacteriaceae | bioRxiv https://www.biorxiv.org/content/10.1101/2025.09.30.679422v1?rss=1

How the twin-arginine translocase (Tat) system manages to transport folded proteins across membranes without any leaks? To answer this fundamental question we solved the first structure of TatB3C3 complex with bound cargo. Please check out new preprint!
t.co/962Kj9pt6F

Heading to the Austrian Cryo-EM Symposium in November? Let's catch up! We'll be on hand to share how freely diffusing smFRET can complement this already exquisitely detailed technique #cryoEM #smfret #singlemolecule

Join us for the Austrian Cryo-EM Symposium Nov 11–12 at @istaresearch.bsky.social!

Top speakers, cutting-edge cryo-EM, and a chance to explore Vienna & the ISTA campus.

Register now 👉 cryoem-symposium.pages.ist.ac.at #cryoEM #teamtomo

Looking for a new approach to studying or eliminating phages? Check out our study introducing anti-phage ASOs (antisense oligos) out in @Nature today. nature.com/articles/s4158…

A conserved PIWI silencing complex detects piRNA-target engagement pubmed.ncbi.nlm.nih.gov/40912244/ #cryoEM

They are inaccurate/disagree with those in the pdb report. Might have used a different model iteration for the stats vs the deposited one. There are also a couple of massive typos (0.143 FSC used for map-to-model instead of 0.5, favoured and disallowed both 89.67%)

The stats in the SI are much better than those on the PDB (<1% disallowed rotamers, clashscore ~20 etc) i.e. false. The map also has awful anisotropy, but there is sadly a precedent for this particular complex dating back to a 2018 ms from others. Total failures of peer review and a sad day for EM

Registration is now open! Please share & repost!

...Beata Turonova, Maya Topf, Florian Wilfling, & Manuela Hospenthal, organized by myself, @aliciakmichael.bsky.social @haselbachlab.bsky.social @schurlab.bsky.social Clemens Plaschka & Thomas Heuser, between @impvienna.bsky.social @istaresearch.bsky.social and @vbcscitraining.bsky.social

Thrilled to announce the nexy Austrian Cryo-EM Symposium, taking place 11th-12th November at @istaresearch.bsky.social, with speakers inc. @grigoriefflab.bsky.social, @oliveiramann.bsky.social, @bjgreber.bsky.social @svenklumpe.bsky.social @sebastianglatt.bsky.social ‪‬https://tinyurl.com/cryo2025

🦠🧍‍♀️From bacterial to human immunity.

We report in @science.org the discovery of a human homolog of SIR2 antiphage proteins that participates in the TLR pathway of animal innate immunity.
Co-led wt @enzopoirier.bsky.social by D. Bonhomme and @hugovaysset.bsky.social

www.science.org/doi/10.1126/...

Temperate phages enhance host fitness via RNA-guided flagellar remodeling Bacterial flagella drive motility and chemotaxis while also playing critical roles in host-pathogen interactions, as their oligomeric subunit, flagellin, is specifically recognized by the mammalian immune system and flagellotropic bacteriophages. We recently discovered a family of phage-encoded, RNA-guided transcription factors known as TldR that regulate flagellin expression. However, the biological significance for this regulation, particularly in the context of host fitness, remained unknown. By focusing on a human clinical Enterobacter isolate that encodes a Flagellin Remodeling prophage (FRφ), here we show that FRφ exploits the combined action of TldR and its flagellin isoform to dramatically alter the flagellar composition and phenotypic properties of its host. This transformation has striking biological consequences, enhancing bacterial motility and mammalian immune evasion, and structural studies by cryo-EM of host- and prophage-encoded filaments reveal distinct architectures underlying these physiological changes. Moreover, we find that FRφ improves colonization in the murine gut, illustrating the beneficial effect of prophage-mediated flagellar remodeling in a host-associated environment. Remarkably, flagellin-regulating TldR homologs emerged multiple times independently, further highlighting the strong selective pressures that drove evolution of RNA-guided flagellin control. Collectively, our results reveal how RNA-guided transcription factors emerged in a parallel evolutionary path to CRISPR-Cas and were co-opted by phages to remodel the flagellar apparatus and enhance host fitness. ### Competing Interest Statement M.W.G.W. is a co-founder of Can9 Bioengineering. S.H.S. is a co-founder and scientific advisor to Dahlia Biosciences, a scientific advisor to CrisprBits and Prime Medicine, and an equity holder in Dahlia Biosciences and CrisprBits. A patent application has been filed related to this work (PCT Patent Application No. PCT/US24/40027). The remaining authors declare no competing interests. National Science Foundation, https://ror.org/021nxhr62, DGE-2036197, CAREER 2239685 National Institutes of Health, NIH DP2AI177904, R01CA259634, U24GM129539 Spain Ministry of Science Innovation and Universities Grant, PID2023-147463NB-I00 Simons Foundation, SF349247 Kinship Foundation Pew Biomedical Scholarship Irma T. Hirschl Career Scientist Award Howard Hughes Medical Institute Columbia University Irving Medical Center Dean’s Office Vagelos Precision Medicine Fund

Temperate phages enhance host fitness via RNA-guided flagellar remodeling | bioRxiv https://www.biorxiv.org/content/10.1101/2025.07.22.666180v1

📢Preprint out!
Excited to share my final work from the @soreklab.bsky.social!

We mined phage dark matter using structural features shared by anti-defense proteins (viral tools that help phages bypass bacterial immunity) to guide discovery.

Found 3 new families targeting immune signaling!

Structural motif search across the protein-universe with Folddisco https://www.biorxiv.org/content/10.1101/2025.07.06.663357v1

Evolutionary repurposing of a DNA segregation machinery into a cytoskeletal system controlling cyanobacterial cell shape Bacteria, despite their diversity, use conserved cytoskeletal systems for their intracellular organization. In unicellular bacteria, the ParMRC DNA partitioning apparatus is well known for forming act...

One of the most exciting discoveries from our lab so far is now online as a preprint!

Read a story on how the ParMR and Min systems started to collaborate to create the CorMR cytoskeleton, which now controls cell shape in multicellular cyanobacteria:
www.biorxiv.org/content/10.1...

Visualization of a multi-turnover Cas9 after product release - Nature Communications Streptococcus pyogenes Cas9 is perhaps the most widely used CRISPR-Cas enzyme. Here, cryo-EM structures provide insight into the conformational landscape of Cas9 under multi-turnover conditions, sugge...

Absolutely brilliant work by @kaitlynakiernan.bsky.social from my former advisor David Taylor's lab: 25 structures from one kinetics-guided cryo-EM dataset, including the elusive post-cleavage dissociated product state www.nature.com/articles/s41...

Origin and Evolution of Bacterial Periplasmic Force Transducers Abstract. In double-membraned bacteria, non-equilibrium processes that occur at the outer membrane are typically coupled to the chemiosmotically energized

Origin and Evolution of Bacterial Periplasmic Force Transducers | Molecular Biology and Evolution | Oxford Academic https://academic.oup.com/mbe/article/42/6/msaf138/8156694?login=false

1/10 New pre-print(s) from the Sternberg Lab in collaboration with Leifu Chang's Lab! We uncover the unprecedented molecular mechanism of CRISPR-Cas12f-like proteins, which drive RNA-guided transcription independently of canonical promoter motifs.
Full story here:
www.biorxiv.org/content/10.1...

Job details Job details

🚨 We're hiring! Join our excellent Electron Microscopy Facility at @istaresearch.bsky.social as an a Cryo-EM Specialist, providing support for groundbreaking research in a fantastic environment: ist.ac.at/en/job/?titl... #CryoEM #MicroscopyJobs #ScienceCareers

Elucidating the mechanisms of action and evolutionary history of phage anti-defence proteins Phages and bacteria are locked in a molecular arms race, with phage anti-defence proteins (ADPs) enabling them to evade bacterial immune systems. To streamline access to information on ADPs, we develo...

Very excited to share our preprint on a new resource: the Encyclopaedia of Viral Anti-Defence Systems (EVADES)! This is the main result of my PhD at ‪EMBL-EBI (@ebi.embl.org)‬
and the University of Cambridge (@cam.ac.uk‬)! 🔗 www.biorxiv.org/content/10.1... 🧵1/n"

How to measure and evaluate binding affinities Simple guidelines and a checklist are provided for performing high-quality equilibrium binding measurements.

Even exclusively using reported apparent Kd would be tricky… elifesciences.org/articles/57264

Online Now: Structural basis for OAS2 regulation and its antiviral function Online now:

West African–South American pandemic Vibrio cholerae encodes multiple distinct phage defence systems - Nature Microbiology The West African–South American lineage of Vibrio cholerae contains multiple distinct anti-phage defence systems that provide resistance to various phage families, including vibriophage ICP1, a key pr...

Exciting news!! Our latest paper is out in Nat. Microbiol. @natmicrobiol.nature.com

We show that a sub-lineage of 7th pandemic V. cholerae has acquired mobile genetic elements packed with phage defense systems—rendering it multi-phage resistant 😳 ..... 1/3

www.nature.com/articles/s41...

🧬🦠🧫 @science.org RNA-mediated CRISPR-Cas13 inhibition through crRNA structural mimicry | Science www.science.org/doi/10.1126/... meeskelab.org bit.ly/sustecheducnJiaLab #CRISPR #RNA

Advancing RNA phage biology through meta-omics Abstract. Bacteriophages with RNA genomes are among the simplest biological entities on Earth. Since their discovery in the 1960s, they have been used as i

I'm happy to share the first publication from my lab @hoerlab.bsky.social, now out in @narjournal.bsky.social! I take a look at the biology of RNA phages, focusing on how meta-omics methods are discovering new RNA phage families and bacterial defense strategies.

#PhageSky

doi.org/10.1093/nar/...

We describe this beautiful mechanism in our preprint:
www.biorxiv.org/content/10.1...
Huge thanks to all co-authors — and especially to my advisor, Andrey Kulbachinskiy — for invaluable support and collaboration!!!

🚨👉 Please check our recent work on bacterial cell division. In situ Cryo-ET reveals the cellular function of the penicillin binding protein 1b supported by AFM, live-cell imaging, in silico AlphaFold proteome screen and TIRFM. Hope you enjoy the read! #teamtomo #cryo-ET ❄️🔬🐎 big thanks to the team!