Baptiste Darracq

Uridine as a potentiator of aminoglycosides through activation of carbohydrate transporters Uridine boosts aminoglycoside treatment efficiency against antibiotic-susceptible as well as antibiotic-resistant E. coli strains.

So excited our antibiotic potentiation story is out 🤩 Led by the extraordinary @manonlang.bsky.social with @fox-science.bsky.social & @amazeld.bsky.social +amazing collaborators @immunobladder.bsky.social @imaneelmeouche.bsky.social 🦠 We believe it can make a difference in #AMR infections!

Bacteriophages infecting an Escherichia coli bacterium. Credit: Institut Pasteur/Chantal Le Bouguénec (Pathogenic Gram-Positive Bacteria Biology Unit) and Laurent Debarbieux (Molecular Biology of the Gene in Extremophiles Unit). Imaging by Perrine Bomme, Ultrastructural Microscopy Platform. Colorization by Jean-Marc Panaud.

🧬 Bacteria fight both antibiotics and viruses with the same genetic tool: integrons!

New study (Institut Pasteur, CNRS, Université Paris Cité & Montréal): ~10% of gene cassettes may defend against phages.

🛠️ One step closer to smarter therapies.

🔗 www.pasteur.fr/en/research-...

😜😜 Thanks Basile

Sedentary chromosomal integrons as biobanks of bacterial antiphage defense systems Integrons are genetic systems that drive bacterial adaptation by acquiring, expressing, and shuffling gene cassettes. While mobile integrons are well known for spreading antibiotic resistance genes, t...

At least 10% of the V. cholerae integron cassettes have novel antiphage activities (see below). Considering that there are 25,000 distinct cassettes of unknown function, integrons constitute an extraordinary and almost inexhaustible reservoir of antiphage functions!

Our paper on how integrons are biobanks of novel minimal defense systems is now out www.science.org/doi/10.1126/... Two main conclusions on this excellent work led by @eloilittner.bsky.social @baptistedarracq.bsky.social 1/n

Sedentary chromosomal integrons as biobanks of bacterial antiphage defense systems Integrons are genetic systems that drive bacterial adaptation by acquiring, expressing, and shuffling gene cassettes. While mobile integrons are well known for spreading antibiotic resistance genes, t...

Our paper is published back2back with one from @amazeld.bsky.social and @epcrocha.bsky.social labs where @baptistedarracq.bsky.social, @eloilittner.bsky.social and co. show that Sedentary Chromosomal Integrons are biobanks of phage defense systems. www.science.org/doi/10.1126/...

Mobile integrons encode phage defense systems Integrons are bacterial genetic elements that capture, stockpile, and modulate the expression of genes encoded in integron cassettes. Mobile integrons (MIs) are borne on plasmids, acting as a vehicle ...

🧪
Finally out after peer review, our work showing that "Mobile #Integrons carry Phage Defense Systems" is now published in Science 🎉

Short 🧵
www.science.org/doi/10.1126/...

Mobile integrons encode phage defense systems Integrons are bacterial genetic elements that capture, stockpile, and modulate the expression of genes encoded in integron cassettes. Mobile integrons (MIs) are borne on plasmids, acting as a vehicle ...

Have also a look at our back-to-back study for mobile integrons by Nicolas Kieffer from @jaescudero.bsky.social group !
www.science.org/doi/10.1126/...
+ a similar story in V. parahaemolyticus by @landongetz.bsky.social from @themaxwelllab.bsky.social
www.nature.com/articles/s41...

An enormous thanks for the great co-first author @eloilittner.bsky.social and for our supervisors @celineloot.bsky.social @epcrocha.bsky.social @amazeld.bsky.social @fredoleroux.bsky.social. Many thanks to all co-authors !!

On the bioinformatic side, eloilittner.bsky.social found a diverse arsenal of anti-phage defenses in SCIs. Strikingly, systems in integrons are always compact (< 3 genes), and smaller than their homologs outside integrons (likely due to cassette size constraints)

The integron of our favorite model Vibrio cholerae was mostly “dark matter” as most cassettes had no known role. We found this intriguing and cloned 88 cassettes, testing them for phage resistance. We found 16 defensive cassettes and named the systems after gallic mythology

Sedentary chromosomal integrons as biobanks of bacterial antiphage defense systems Integrons are genetic systems that drive bacterial adaptation by acquiring, expressing, and shuffling gene cassettes. While mobile integrons are well known for spreading antibiotic resistance genes, t...

White smoke, we have a new pope and also 16 new anti-phages systems in sedentary integrons (SCIs) !
In collaboration with the Rocha lab, we show in our new paper that cassettes of these large platforms encode many known anti-phage defenses, and uncovered 16 new ones.
www.science.org/doi/10.1126/...

Alt : Structure of the apo Lamassu protein complex. Schematic model of the active LmuA tetramer nuclease (top right). Lamassu icon (top left).

Glad to share the work of @yli18smc.bsky.social and co on Lamassu, a bacterial defense system related to Rad50/Mre11 (RM). While RM carefully trims DNA ends for repair, Lamassu chops up the host chromosome. Our study reveals how it is regulated to minimize damage, activating only during infection.