SnapShot: Bacterial Immunity
@Nitzan_T
masterfully organized current knowledge on bacterial immune systems into a single page graphics
Out today
@CellCellPress
:
Bacterial origins of human innate immune mechanisms
Tanita Wein skillfully summarized current knowledge on how key components our own immune system evolved from bacterial anti-phage defenses
Out today in Nature Reviews Immunology
Preprint: We report the discovery of >20 new bacterial defense systems! Some with homology to human immune genes
A 4-year effort of the entire Sorek Lab, led by talented
@AdiMillman
,
@Curiousphage
, Azita Leavitt,
@shany_doron
and many more
After more than three decades of mystery, we are happy to report that we discovered the function of some of the coolest bacterial elements - retrons.
Retrons function as anti-phage defense systems!
See our new preprint
@AdiMillman
@AudeBer
@AAvihail
On the origin of immunity
Remarkable similarities between human and bacterial immune systems.
Cyclic GMP–AMP signalling protects bacteria against viral infection
Congrats CBASS team! Daniel Cohen
@AdiMillman
@GilAmitai
@shany_doron
#cGAS
-
#STING
Happy to see our paper out
@nature
:
Phages confiscate signaling molecules produced by immune TIR proteins to cancel host immunity
Structure of anti-defense "sponge" protein reveals a new class of antiviral signaling molecules: glycocyclic-ADPR (gcADPR)
Happy to share our paper out today
@nature
:
TIR domains in bacteria protect from viruses by producing unique signaling molecules
A surprising parallel between bacterial and plant immunity
Congrats
@gaofir
,
@GilAmitai
and coauthors!
New in Nature: The evolutionary origin of the human STING protein is the bacterial CBASS anti-phage system.
"STING cyclic dinucleotide sensing originated in bacteria"
Out
@CellCellPress
: Together with the Kranzusch lab, we characterized RADAR, a giant immune machine that blocks viruses via adenine deamination
A complex of 96 protein subunits, 4 times heavier than the ribosome
Congrats
@B_DuncanLowey
and
@Nitzan_T
!
A family of bacterial enzymes produce antiviral molecules to fight phage! These enzymes form the origin of Viperin, an important human antiviral gene.
Check out our new paper:
Systematic discovery of phage determinants that trigger bacterial immunity
Super talented
@AAvihail
💫studied ~200 phage mutants that escape numerous defense systems
Revealing key principles on how bacterial immune systems sense phage invasion🧫🧪
Out today
@cellhostmicrobe
: An expanded arsenal of bacterial immune systems
Even if you previously read the preprint, don’t miss a major new result on the bacterial SEFIR domain, a homolog of human immune domains
A thread 🧵 1/9
Proud to share our latest discovery: Bacteria conjugate ubiquitin-like proteins to interfere with phage assembly
A new concept in antiphage immunity, and a mechanism for ISG15-like antiviral defnese in bacteria. Big congrats to talented
@Jens_Hoer
!
A 🧵
Now in Cell: Bacterial retrons function in anti-phage defense !
Excited to solve a decades-old mystery on the function of these RNA/DNA hybrid molecules
Congrats
@AdiMillman
@AudeBer
@AAvihail
!
A link between bacterial and plant immune systems! TIR proteins protect from phage by generating signaling molecules that trigger cell death
Similar molecule (cADPR variant) is produced by plant TIRs in response to pathogens
Our paper:
Congrats
@gaofir
!
Honored and humbled to receive the Max Planck Humboldt Research Award for 2023. Thank you to the Humboldt Foundation and the Max Planck Society for this honor! Excited towards collaborating with
@JoergLab
at
@Helmholtz_HIRI
and
@v_hornung
in LMU Munich
Glückwunsch an den Mikrobiologen Rotem Sorek zum Max-Planck-Humboldt-Forschungspreis 2023! 👏🎉 Die Max-Planck-Humboldt-Medaillen erhalten Amy Buck und Kandice Tanner.
@maxplanckpress
@SorekLab
@WeizmannScience
The first symposium on the "beyond CRISPR" immune system of bacteria: Registration open!
Feb 28th-Mar 2nd at the Weizmann Institute, Israel
A fantastic line up of speakers + talks selected from abstracts. We have limited space, hurry up and register!
Pyroptosis is conserved between human and bacteria: caspase-activated gasdermins form pores and protect bacteria from phage
Fantastic collaboration with the Kranzusch lab, now out in
@ScienceMagazine
Congrats
@TanaWein
&
@algejohn
!
New defense system alert!
Pycsar: Pyrimidine Cyclase System for Antiphage Resistance
cCMP and cUMP are new immune signaling molecules!
Congrats
@Nitzan_T
&
@morehouse_ben
! A fantastic collaboration with the Kranzusch lab
I can't wait for the 2024 symposium on the "beyond CRISPR" immune system of bacteria, which will take place in Boston on April 16-18, 2024. Save the date!
Thank you to the HFSP Nakasone award, this is a great honor.
Stoked and humbled to be included in the same list as the amazing scientists who received this award in the past
News on the Zorya defense system: anchors to the peptidoglycan and detects membrane disruption by phage. It has a flagella-motor-like device that rotates once activated. So cool! I've been waiting for insights on Zorya since we first described it 5 years ago. Congrats Tylor&co!
Immune NLR genes are conserved in bacteria and provide protection against phage. An incredible study.
These bacterial NLRs recognize PAMPs that are conserved between phages and herpes viruses!
Forget Illustrator. This is the best rendition of the arbitrium communication system ever! Beautiful farewell gift made by
@erez_zohar
#bioart
(we'll miss you!)
Antiviral defense via nucleotide depletion in bacteria
New defense proteins, dCTP deaminase and dGTPase, degrade nucleotides during infection, starving the phage & halting replication
Similar protein (SAMHD1) protects human from HIV
Congrats
@Nitzan_T
!
Out now
@Nature
: our two joint papers with the amazing Kranzusch lab. We found how phages overcome the defense systems Gabija, Hachiman and Thoeris
Congrats
@ErezTzvi
,
@sadie_antine
, Azita Leavitt,
@amitai_gil
and coauthors
By analyzing groups of genomically similar phages that showed differential sensitivity to bacterial defense systems, we discovered two anti-Gabija genes (gad1 and gad2), an anti-Thoeris gene (tad2) and an anti-Hachiman gene (had1).
CARD domains in bacteria!
CARD domains are essential for recruitment of caspases during inflammasome activation and gasdermin-mediated pyroptosis in humans. We now found that CARD domains mediate anti-phage defense in bacterial gasdermin systems
Congrats
@TanaWein
&
@algejohn
!
I am beyond excited to share our new preprint!🤩
We find that CARD domains are an ancient component of innate immune systems conserved from bacteria to human, and that they are essential for gasdermin-mediated defense in bacteria!
@SorekLab
Kranzusch lab
We describe a new family of immune protein domains that break ATP to abort viral infection
They protect bacteria against phages and also likely function in animal immunity
Found in CBASS/NLR/pAgo, plus a new system: Detocs
Congrats
@FrancoisRousset
!
I’m very excited to share the first results of my postdoc
@SorekLab
🥳🤩🚨
We report a new family of immune effectors that is conserved across the tree of life.
Was honored and moved by the heartwarming ceremony in Berlin yesterday. Thank you to the Max Planck Society and the Humboldt Foundation! More than ever I am convinced that science is the strongest universal bridge to connect people and cultures
Our paper out today
@NatureMicrobiol
:
Sirtuin (SIR2) domains in bacteria function in many anti-phage defense systems
These domains degrade NAD+ once phage is sensed, depleting the cell of energy and halting phage replication
Mechanism of the Hachiman immune system finally deciphered
A beautiful study from the Doudna lab shows that Hachiman is a genome integrity sensor
Congrats
@doudna_lab
and colleagues!
A new class of immune signaling molecules generated by TIR domains: histidine conjugated to ADP-ribose
Check out our preprint:
A fantastic collaboration with the Tamulaitiene and Kranzusch labs
A 🧵 1/9
Preprint: Phages reconstitute NAD+ to counter bacterial immunity
Many bacterial immune systems degrade NAD+ to deplete the cell of energy, halting phage replication
Ilya Osterman now discovered that phages can rebuild NAD and overcome defense
Ever tried crossbreeding your phages? Check out our new study by
@GarbJeremy
:
Phage mating helped us solve the mechanism of defense-associated sirtuins (DSR) – a large family of anti-phage defense systems
Many phages are known to encode tRNAs of their own. Now Isaev, Wiedenhaft, Bikard and co show that these tRNAs enable phages to evade bacterial defense systems. A beautiful story, showing that the PARIS defense system cleaves host tRNAs when it detects infection. Congrats!
Why do phages encode tRNAs? It aids in defeating tRNA-targeting immune systems. We provide structure and mechanism for the PARIS defense and show how it cleaves host tRNA upon trigger sensing. Stikingly, the non-cleavable tRNA of T5 supports the infection.
Out today
@CellCellPress
: a new family of immune proteins that deplete the cell of ATP and dATP when viral infection is recognized
This immune mechanism is conserved from bacteria to animals
Congratulations
@FrancoisRousset
!
We just posted a preprint proposing a new role for the 50-year old conundrum of phage-encoded tRNAs: insensitivity to host tRNA depletion by anticodon nucleases (e.g. VapC). Great data analysis and hypothesis building by
@DaanFvdBerg
A recording of my recent lecture at the NIH, summarizing our current understanding on the immune system of bacteria: new mechanisms, evolutionary links to the human immune system, how phages fight back, and open questions
Can't wait for the first Symposium on the Immune System of Bacteria, happening at the Weizmann Institute two weeks from now!
Looking forward to welcoming you all and hearing of exciting new discoveries in the field!
Registration for the 2024 Boston Symposium on the Immune System of Bacteria is now open - an exciting program with a fantastic lineup of speakers! Additional talks will be selected from submitted abstracts
I can't wait for the 2024 symposium on the "beyond CRISPR" immune system of bacteria, which will take place in Boston on April 16-18, 2024. Save the date!
New immune genes in humans are identified based on conservation with bacterial anti-phage defense systems! 🔥
Congrats
@audeber
and team for this important discovery!
In a new preprint, we report that recently discovered anti-phages systems (Mokosh, Eleos, Lamassu…) have eukaryotic homologs.
We harnessed this conservation to discover novel defense mechanisms in humans.
@howmanyernest1
@gaofir
@EnzoZ_P
@AudeBer
Love this pic. The entire lab exploring and annotating new defense systems, in the "Defense 2.0 Blitz" week back in the summer of 2018. So many discoveries emerged from this session: CBASS, retrons, and now the recent addition of 21 new systems 🤩
Since these were way too many to test we had to prioritize. This is where the whole Sorek lab joined the effort and in the first "Sorek lab hackathon", helped analyze and select systems for verification.
3/7
A belated tweet: Our paper on how bacterial immune systems sense phage invaders was published last Friday
@CellCellPress
Talented Avigail Stokar-Avihail, who masterfully led this study, explains it in the thread below
Congrats
@AAvihail
& coauthors!
I am excited to share with you the final version of my work
@SorekLab
studying
💠How bacterial immune systems sense phage infection💠
Published now in
@CellCellPress
🍻
See thread below for a recap and highlights added during the review process ⬇️
1/11
BiomX announces positive topline results from phase 1b/2a trial, testing phage cocktail against chronic infections in CF patients
Some patients, who suffered from P. aeruginosa infection for >10 years, tested negative for the bug after phage treatment
It is indeed an amazing anti phage defense system alright, but not CRISPR. This is a statue of Lamassu, the god protector of household in the Assyrian mythology. Lamassu is a family of defense systems present in ~10% of bacterial genomes, mechanism yet to be deciphered
Phages inhibit bacterial TIR signaling using "sponge" proteins
Bonus: TIR-derived signaling molecule revealed!
A super fun collaboration with the Kranzusch lab! Congrats Azita Leavitt,
@ErezTzvi
,
@amitai_gil
, Allen Lu!
Super excited to share our new preprint, discovering an anti-Thoeris protein and an immune signaling molecule produced by both plants and bacteria! A super fun and productive collaboration with the
@SorekLab
and the Kranzusch lab.
Out today: Bacteria, like humans, manipulate the cellular nucleotide pool to curb viral infection
Originally posted in bioRxiv, now with new data
@NatureMicrobiol
Read the thread by Nitzan Tal, discoverer and leading author 💫
Excited to share the final version of our story on 🌟 how bacteria use nucleotide depletion to fight viral infection🌟, now
@NatureMicrobiol
!
A brief recap, what was added, and some thoughts below 🦠🤩
Multiple new classes of phage proteins that inhibit bacterial immunity:
Tad2 intercepts immune signals of defense TIR domains
Gad1 traps the Gabija defense system in a cage
And more...
Fun collaborations with the Kranzusch lab!
Two beautiful papers determine the structure of the anti-plasmid defense system Wadjet
Structures explain how circular plasmid DNA is recognized and cleaved. Fascinating!
Congrats
@Gruber_Lausanne
and
@_KevinCorbett
The Weizmann symposium on the Immune System of Bacteria: abstract submission deadline is next week, Jan 10th!
Best abstracts will be selected for short talks
We also have a few remaining slots for registration
The first symposium on the "beyond CRISPR" immune system of bacteria: Registration open!
Feb 28th-Mar 2nd at the Weizmann Institute, Israel
A fantastic line up of speakers + talks selected from abstracts. We have limited space, hurry up and register!
Interesting: The BREX protein BrxL is not a protease, despite sequence and structure homologies to Lon proteases
BREX was the first 'new' antiphage defense system discovered based on presence in defense islands, and its mechanism is still not understood
Very interesting paper from the
@edzewestra
lab, showing that in conditions dictating longer phage replication cycles, cells are more likely to acquire CRISPR immunity. Relevant to many non-lab environments in which bacteria naturally grow slowly
Finally, insight on the function of the Zorya immune system. A fascinating system sharing evolutionary origin with bacterial flagella. Have been waiting to learn more about this system for five years now, since we first reported it in our Doron 2018 paper
Exciting talk by our friend and colleague Nicholas Taylor
@NMITaylorLab
on the Zorya anti-phage defense system - bacterial immunity is truly a gateway to molecular biology from the dark side of the moon!
Preprint: We studied defense islands in 1350 E coli genomes, involving >60 types of defense systems
The vast majority of defense systems are carried on mobile genetic elements, that integrate in dedicated genomic positions
Congrats
@dinahoch
!
My turn! 🙋🏼♀️ Come read my FIRST first-author paper of my PhD
@SorekLab
, on the hot 🔥 topic of defence islands! 🏝
The defence island repertoire of the Escherichia coli pan-genome
Just learned that the glyco-cyclic ADPR immune signaling molecules we discovered, 2’ cADPR and 3’ cADPR, are available as purified products at Biolog:
Very useful for researchers studying immune signaling in bacteria and plants
So many novel antiphage systems out there! Hard to keep up with the pace of discoveries? We reviewed for
@NatureRevMicro
the highly diverse antiphage defence systems of bacteria; from molecular mechanisms to evolutionary drivers of such diversity.
Blurring the lines between plasmids and viruses
A plasmid from an Antarctic haloarchaeon uses specialized membrane vesicles to disseminate and infect plasmid-free cells
In response to phage infection, bacterial gasdermins are activated to form membrane pores
Here is a time lapse microscopy of cells infected by phage T6. Gasdermin in these cells is fused to GFP. Activated gasdermins aggregate & perforate the membrane (pink is propodium iodide)
Studying the gasdermin system at the single-cell level in vivo we find that gasdermin is proteolytically cleaved during infection leading to gasdermin aggregation and membrane permeation.
A eukaryotic-like ubiquitination machinery in bacteria! Beautiful structures from the Corbett lab.
This machinery defends bacteria against phage infection by targeting phage structural proteins and interfering with virion assembly
I'm thrilled to share the latest work from my lab, showing that a bacterial anti-phage immune system encodes a ubiquitination pathway strikingly similar to our own! (1/12)
Gasdermins, important players in human immunity, are also present in bacteria
As the human gasdermins, bacterial ones are activated by caspases to form membrane pores
Congrats
@TanaWein
@algejohn
! Super fun collaboration with the Kranzusch lab
Preprint:
Look who’s talking!
Discovery of numerous communication systems in a single bacterium-Paenibacilli are such social microbes!
@MayaVoichek
shares her story in our lab’s first
#preprint
Peptide-based quorum sensing systems in Paenibacillus polymyxa
A bit lost with all the new anti-phage systems out there? We developed DefenseFinder, a tool to detect all known anti-viral systems in bacterial genomes and conducted a large scale analysis on the anti-viral arsenal of prokaryotes. See more below ! (1/9)
@HtChi221
After a lot of hard work with confusing and negative results, Haotian solved the puzzle and revealed a new signalling molecule, SAM-AMP, for antiviral defence. We hope you enjoy the paper!
Proud to share our new work
@CellCellPress
. We identified and experimentally validated
#microbiome
strains contributing to IBD flareups across geography (4 countries), and developed a first-of-its kind combination phage therapy
Preprint: Human SARM1 can produce gADPR molecules as minor products
SARM1 is a conserved TIR-domain protein known as an NAD-degrading enzyme. We now show that it can also produce signal molecules. This might be important in human neurobiology. A 🧵 1/9
Type II Lamassu defense system (also called DdmABC in V. cholerae) is triggered by DNA stem-loop hairpin structures
Structures are suggested to form during phage and plasmid replication from single-stranded or damaged DNA
Interesting preprint from the Mekalanos lab!
Phage single-strand DNA binding (SSB) proteins are, in many cases, essential components of the phage replication apparatus. Many defense systems seem to sense the phage SSB as a signature of infection. Here is another example 👇
Hna confers
#phage
resistance.
#Bacteriophage
defense system “Hna” consisting of single predicted helicase/nuclease confers protection by abortive infection. Hna homologs present in array of
#bacteria
, including medically or agriculturally relevant species
Wow, this is a truly revolutionary method!
Allows measuring gene expression in bacteria at the single cell level, and also records the position of the cell within the culture (e.g. biofilm).
Congrats
@Danidiin
!! 💫
If you ever wanted to know which collection of anti-phage defense systems your favorite bacteria encodes, PADLOC is the tool for you
A nice analysis of defense systems distribution across microbes, plus discovery of some new ones!👇
Cool study from the
@joeBondyDenomy
lab, showing how phages evade bacterial cGAS immunity using dedicated sponge proteins that sequester cGAMP
Do viruses that infect humans use a similar mechanism to evade cGAS-STING? I bet they do
Congrats
@ErinHuiting
and
@joeBondyDenomy
!
Our latest CBASS story from the
@joeBondyDenomy
lab has arrived! 🙌Through a serendipitous collaboration with Yue Feng's lab, we uncovered an anti-CBASS protein that ‘sponges’ up a broad spectrum of cyclic dinucleotides.
1/14
Preprint: A giant protein complex drives anti-phage defense
Multi-megadalton complex, formed by the RADAR system, deaminates adenosines into poisonous nucleotides during infection
A wonderful collaboration with the Kranzusch lab, congrats
@B_DuncanLowey
and
@Nitzan_T
!
I’m excited to share our preprint describing the structure of the RADAR antiphage defense system! This was such a fun collaboration with the wonderful
@Nitzan_T
and the
@SorekLab
! A short thread about this huge machine (1/8)
Take a look at these beautiful electron microscopy images taken by Jens together with
@ShaLGW
. In these images, gold-labeled antibodies (black dots) mark the ubiquitin-like protein conjugated to the tip of the phage tail
I am thrilled to announce that I will soon open my independent group at
@CIRI_Lyon
🤩
My team will develop new approaches to explore the molecular arms race between phages and bacteria 🦠🧐
Join us in this new adventure in the beautiful city of Lyon !
Congratulations to Fatima Hussain
@fatiays
and
@JavierDubert
on their new paper in Science describing surprising ways how bacteria in the wild defend themselves against phage. See also perspective by Perspective by Meaden and Fineran.
Interesting implications for bacterial defense systems. "We demonstrate that intracellular defense systems are major determinants of phage host range and that overall phage resistance scales with the number of defense systems in the bacterial genome."
Fresh out of the oven! Panphage immunity in Pseudomonas by
@AnaRitaMCosta
, my former MSc student Daan van den Berg, and Jelger Esser from the
@StanBrouns
lab. Very happy to have been able to participate and see the impact of the
@fagenbank
in research.