Cryptic Prophage (phage 🧬🪤 in 🦠)
crypticprophage.bsky.social
Cryptic Prophage (phage 🧬🪤 in 🦠)
@crypticprophage.bsky.social

TA systems stop phages (discovered '96), phages create persisters (discovered '23), E. c. CRISPR regulates cryptic prophages (discovered '21), indole = inter-kingdom signal, AI2 increases biofilm & TqsA exports (Thomas K. Wood, endowed prof, H113, 351 pub) .. more

Biology 57%
Environmental science 18%
Pinned
academic.oup.com/nar/article/...
We discovered a new, wide-spread phage defense system based on serine recombinase PinQ in E. coli cryptic prophage Qin that inverts 1,797 bp in another cryptic prophage, e14, to encode two chimeric proteins that block adsorption of T2 phage. @NAR_Open
Adsorption of phage T2 is inhibited due to inversion of cryptic prophage DNA by the serine recombinase PinQ
Abstract. Recombinases catalyze site-specific integration, excision, and inversion of DNA and are often found adjacent to anti-phage system genes clustered
academic.oup.com

Congratulations to Joy for all of her hard work and to all the visitors to my lab including Daniel, Rodolfo, and Michael, who had an incredible impact and thanks to Maria!

Thanks also to the three reviewers that provided excellent insights to improve the paper.

Reposted by Thomas K. Wood

nature.com/articles/s41564-025-02124-2
BPOET: 1st high-throughput search (10,000 cmpds), resuscitates persisters (2020) with mechanism of activating hibernating ribosomes via 23S rRNA pseudouridine synthase RluD (E. coli, doi:10.1111/1462-2920.14828), cited, but not in context vs. new search:

Uracil first shown 2009 to be a QS signal in P. a. & UMP path important for QS & virulence. Moreover, 5-fluorouracil is a potent QS quencher & is the first QQ compound used commercially (for catheters). Uracil also is a signal in the Drosophila GI tract.

Using DefenseFinder misses nearly all of the toxin/antitoxin systems; i.e., the most prevalent phage defense system is missing to a large degree from this database. I recommend running TAFinder or TADB. etc., too, to search for TAs, which likely are anti-phage systems.

Reposted by Thomas K. Wood

#NewResearch

Nasal colonisation by S. aureus is linked with depression in a human cohort and shown in a mouse model to cause decreased serotonin and dopamine in the brain

#MicroSky #Depression

www.nature.com/articles/s41...
Nasal Staphylococcus aureus carriage promotes depressive behaviour in mice via sex hormone degradation - Nature Microbiology
Nasal colonization by Staphylococcus aureus is linked with depression in a human cohort and shown in a mouse model to cause decreased serotonin and dopamine in the brain.
www.nature.com

Reposted by Thomas K. Wood

I am excited to announce a fantastic collaboration! We thank the U.S.-Israel #BSF and the National Science Foundation #NSF for funding our project with Prof. Hadar Ben-Yoav and @crypticprophage.bsky.social. We will be studying #mucin- associated #biofilms using innovative mucin-on-chip systems.

Reposted by Thomas K. Wood

Congratulations Ilana!

doi.org/10.1128/ecos...
Balanced review from Ed Dudley considering whether CRISPR-Cas is active in E. coli K-12. We discovered it silences lysis transcripts from cryptic prophages in 2022 (doi 10.3390/ijms232416195).
The E. coli CRISPR-Cas conundrum: are they functional immune systems or genomic singularities? | EcoSal Plus
The story spanning the first recognition of peculiar repeat sequences in the genomes of Escherichia coli (1), to the functional description of what is today known as CRISPR-Cas, has been detailed in s...
doi.org

nature.com/articles/s41...
On the basis of sex: another important link of toxin/antitoxin systems to the stress response. Here, P. aeruginosa-derived NQNO inhibits N. gonorrhoeae by increasing oxidative stress, activating Zeta1 toxin, without affecting vaginal lactobacilli.
A quinolone N-oxide antibiotic selectively targets Neisseria gonorrhoeae via its toxin–antitoxin system - Nature Microbiology
Pseudomonas aeruginosa-derived 2-nonyl-4-quinolone N-oxide exerts bactericidal effects on Neisseria gonorrhoea via zeta1–epsilon1 toxin–antitoxin activation in vitro and abrogates experimental infecti...
nature.com

biorxiv.org/content/10.1...
We found ubiquitous recombinases from cryptic prophages may invert DNA to form new, chimeric proteins that inhibit phages by blocking adsorption. Congratulations to Joy, Daniel, Rodolfo and Michael for their strong efforts.
Serine Recombinase PinR Inverts Cryptic Prophage DNA to Block Adsorption of Phages
Recombinases catalyze site-specific integration, excision, and inversion of DNA and are found in myriad defense islands; however, their function in phage-defense is unknown as they are frequently dism...
biorxiv.org

Cryptic Prophage (phage 🧬🪤 in 🦠)
(2/2) Not cited: doi:10.1111/1462-2920.14075 where it was shown the few live VBNCs = persisters. Also, there is no proof of differences in dormancy, i.e., no differences in persister cells (enviromicro-journals.onlinelibrary.wiley.com/doi/10.1111/...).
Viable but non‐culturable and persistence describe the same bacterial stress state
Bacteria are often thought of as having two dormant phenotypes: the viable but non-culturable (VBNC) state and the persister state. Here we investigate the relatedness of the two stress-induced pheno...
enviromicro-journals.onlinelibrary.wiley.com

doi.org/10.1016/j.ti...
(1/2) Fantastic summary of flawed research. As published, there are no differences between persisters & the live fraction of VBNCs & one of the clear indications of death is protein aggregation, so increased aggregation simply means the cells are dead.

🧐Yes, indeed, there is a continuum of dormancy: Persisters revive based on ribosomes almost instantaneously with food and VBNCs never revive since they are dead, which is the ultimate dormant state...i.e., protein aggregation = death.

Reposted by Thomas K. Wood

A noncanonical intrinsic terminator in the HicAB toxin–antitoxin operon promotes the transmission of conjugative antibiotic resistance plasmids

in @narjournal.bsky.social by Lin et al.

academic.oup.com/nar/article/...
A noncanonical intrinsic terminator in the HicAB toxin–antitoxin operon promotes the transmission of conjugative antibiotic resistance plasmids
Abstract. Conjugative plasmids, major vehicles for the spread of antibiotic resistance genes, often contain multiple toxin–antitoxin (TA) systems. However,
academic.oup.com

www.sciencedirect.com/science/arti...
🧐106 claims of cell death ('Abi', 'PCD', 'abortosome', 'death') upon phage induction of Hailibu system (DUR4297 DNase + HerA ATPase), but extraordinarily weak data to support claims: just system fails 3 MOI but works at 100X less phage.
DUF4297 and HerA form abortosome to mediate bacterial immunity against phage infection
Immune receptors form higher-order complexes known as inflammasomes in animals and resistosomes in plants to mediate immune signaling. Here, we report…
www.sciencedirect.com

www.sciencedirect.com/science/arti...
Chicken or egg? Looks like toxin/antitoxins were first, and a type III TA system (HEPN RNase toxin inhibited by ncRNA) evolved into CRISPR-Cas13 (RNA-degrading).
Reprogrammable RNA-targeting CRISPR systems evolved from RNA toxin-antitoxins
Despite ongoing efforts to study CRISPR systems, the evolutionary origins giving rise to reprogrammable RNA-guided mechanisms remain poorly understood…
www.sciencedirect.com

academic.oup.com/nar/article/...
Excellent additional proof of the regulatory nature of toxin/antitoxin modules by binding promoters other than the ones that encode the TA locus. Here, MtvT/MvtA decrease conjugation and increase virulence of P. aeruginosa.
A plasmid-encoded inactive toxin–antitoxin system MtvT/MtvA regulates plasmid conjugative transfer and bacterial virulence in Pseudomonas aeruginosa
Abstract. Plasmid-encoded toxin–antitoxin (TA) systems are known for their role in plasmid maintenance via post-segregational killing. Here, we identified
academic.oup.com

www.nature.com/articles/s41...
Results are in-line with the first single-cell persister resuscitation work of 2018 (not cited) which showed many persister cells lyse upon waking due to internalized ampicillin (doi 10.1111/1462-2920.14093).
Limited impact of Salmonella stress and persisters on antibiotic clearance - Nature
Experiments in infected mice and tissue-mimicking chemostats show that resilience of Salmonella against antimicrobial compounds is largely a result of starvation-induced general resilience rather than...
www.nature.com

www.nature.com/articles/s41...
🧐Yes, indeed, there is a continuum of dormancy: Persisters revive based on ribosomes almost instantaneously with food and VBNCs never revive since they are dead, which is the ultimate dormant state...i.e., protein aggregation = death.
Composition and liquid-to-solid maturation of protein aggregates contribute to bacterial dormancy development and recovery - Nature Communications
Recalcitrant infections are often caused by dormant bacteria, including persisters and viable but nonculturable cells. Here, the authors explore how composition and structure of protein aggregates affect dormancy and exit from this state.
www.nature.com

I am sorry to hear that Vivek. I hope the pain diminishes.

www.biorxiv.org/content/10.1...
Most 'novel' systems described here after prediction from machine learning, are related to toxin/antitoxin systems (e.g., DS-11, DS6AB, DS-3, DS-32, HEPN motifs, etc.) cementing the idea that TAs are the most prevalent phage defense system.
DefensePredictor: A Machine Learning Model to Discover Novel Prokaryotic Immune Systems
Anti-phage defense systems protect bacteria from viruses. Studying defense systems has begun to reveal the evolutionary roots of eukaryotic innate immunity and produced important biotechnologies such ...
www.biorxiv.org

Fun read. And yes, persistence (dormancy via ribosome inactivation) should be recognized as an universal state, conserved across kingdoms and for bacteria, like lag, exponential, and stationary phases.

Congratulations and Happy New Year!

www.sciencedirect.com/science/arti...
Yet another phage defense system that detects free DNA ends and provides immunity without causing 'programmed cell death'.
DNA end sensing and cleavage by the Shedu anti-phage defense system
The detection of molecular patterns associated with invading pathogens is a hallmark of innate immune systems. Prokaryotes deploy sophisticated host d…
www.sciencedirect.com

Reposted by Thomas K. Wood

What a great way to end the year! ✨

Today in @cellpress.bsky.social we report the structure and function of the Shedu anti-phage defense system.

tinyurl.com/4crj6dnx

A long 🧵...

www.nature.com/articles/s41...
Another phage inhibition system (Zorya) that does not cause cell death or what has been termed 'abortive infection'. Congratulations to the authors for discerning the lovely mechanism of detecting phage disruption of the cell envelope then DNase activity.
Structure and mechanism of the Zorya anti-phage defense system - Nature
Nature - Structure and mechanism of the Zorya anti-phage defense system
www.nature.com

doi.org/10.1038/s415...
Just my opinion, based on what I consider sound research in a field with much noise due to studying dying cells, but please see the attached list of the usual errors from this lab in their Nature Rev Micro persister review.