@crypticprophage

TAs 🛑 phages ('96), phages ➡️ persisters, E. c. CRISPR 🛑 cryptic prophages, indole=interkingdom signal, AI2 incr biofilm & TqsA exports (Prof. Thomas K. Wood)

 Endowed Professor 3X (H 118)
sites.psu.edu/woodgroup/
Joined February 2022
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biorxiv.org/content/10.64898… (1/2) It took 12 yrs, but we performed the first directed evolution of methyl-coenzyme M reductase (ANME-1 Mcr that captures CH4) by selecting for growth on CH4 in a methanogen forced to reverse methanogenesis.

Engineering Methyl-Coenzyme M Reductase for Enhanced Methane and Carbon Dioxide Capture through...

Methane is a potent greenhouse gas, nearly half of which is consumed anaerobically by anaerobic methanotrophic archaea (ANME) through methyl-coenzyme M reductase (Mcr). However, ANME cannot be grown...

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sciencedirect.com/science/ar… Final version: We created the 1st anaerobic strain that grows on CH4 as a pure culture in 2016 by cloning Mcr from ANME & now we improve it 10X by silencing the chromosomal copy of Mcr in the methanogenic host through RNAi.
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nature.com/articles/s41579-0… Remember, 25 years before Laub's self-citation (ref 30), transcription shutoff was discovered (doi: 10.1128/jb.178.7.2044-2050.1996, JBac 1996), not cited. This is one of the most general methods of phage defense, since most phages highjack transcription.

How bacterial immune systems sense phage infection

Nature Reviews Microbiology - Bacteria deploy diverse immune systems to counter phage infection, yet how these systems sense invasion remains incompletely understood. This Review categorizes...

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This discovery was through Hok/Sok and was the first link of toxin/antitoxin systems to phage defense. journals.asm.org/doi/10.1128…

Exclusion of T4 phage by the hok/sok killer locus from plasmid R1 | Journal of Bacteriology

The hok (host killing) and sok (suppressor of killing) genes (hok/sok) efficiently maintain the low-copy-number plasmid R1. To investigate whether the hok/sok locus evolved as a phage-exclusion...

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biorxiv.org/content/10.64898… Agrees with prior work discovering less fit cells (here, that lack RM), form more persisters (see doi:10.1111/j.1751-7915.2011.00327.x from 2012). Previously, using most-prevalent defense, TAs, more toxic toxin reduces fitness & increases persister cells.

Loss of restriction-modification methyltransferases drives persistence to fluoroquinolones in...

The resurgence of phage therapy has renewed interest in the interplay between phage resistance and antibiotic susceptibility[1][1],[2][2],[3][3] and has stimulated research in the emergent field of...

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doi.org/10.1016/j.cej.2026.1… We created the 1st anaerobic strain that grows on CH4 as a pure culture in 2016 by cloning Mcr from ANME & now we improve it 10X by silencing the chromosomal copy of Mcr in the methanogenic host through RNAi.
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Well done Hyeon-Ji (@hjhwang0822), Ruchira, and Rodolfo (@Larvberg), and Ilke!
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onlinelibrary.wiley.com/doi/… Seems the results herein support that ribosome activity dictates persistence: lag-phase (where there are insufficient ribosomes/growth) most affected by toxin HipA, and HipA directly masks translation (and increases persitence).

Mechanistic insights into HipA‐mediated bacterial persistence: Role of initial cellular states and...

Persistent bacteria subpopulations showing multidrug tolerance pose significant challenges to antibiotic therapy. While the HipBA toxin–antitoxin (TA) system is known to play a role in persister...

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Cryptic Prophage (phage 🧬🪤 in 🦠) retweeted
IMiLI@IMiLImicroSep 17
Happy DAY! Not all bacteria die when antibiotics reach. Some enter a temporary “sleep mode”: persistence, surviving stress without changing their genes. When conditions improve, they wake up and can restart infections—one reason some infections return grupos.eez.csic.es/imili/wp-…
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doi.org/10.1093/molbev/msag2… Authors claim chromosomal TAs do not associate with phage defense islands (arguing they are selfish elements, not phage defense) but indicate they associate with recombinases, which are often themselves phage defenses (doi 10.1093/nar/gkaf1041, NAR 2025).

Acquisition and erosion of toxin–antitoxin systems in bacterial chromosomes

Abstract. Toxin–antitoxin systems are widespread in bacterial genomes. Yet, their integration, persistence, and impact on chromosome dynamics remain unclea

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Authors claimed for decades chromosomal TAs have no physiological role (doi.org/10.1128/jb.00763-19) and have been amply shown to be incorrect.
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doi.org/10.1038/s44259-026-0… Orpheus descending..right overall result (persisters in stasis do not mutate since they are dormant) but beware of all other results as mutations occur during growth, so for any cycling including growth, resucitating persisters mutate LIKE ALL OTHER CELLS.

Selective context, rather than persister cycling alone, drives resistance fixation in Escherichia...

npj Antimicrobials and Resistance - Selective context, rather than persister cycling alone, drives resistance fixation in Escherichia coli

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doi.org/10.1016/j.tim.2026.0… Lovely review of toxin/antitoxin tripartite systems emphasizing their role in phage defense.
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biorxiv.org/content/10.64898… 🥳B. subtilis phage quorum-sensing peptide SAIRGA sensed by host in absence of infection & increases colony biofilm formation. How detected, unknown.

A phage communication peptide alters Bacillus subtilis colony development and promotes sporulation

Temperate Bacillus phages use arbitrium peptides to coordinate lysis–lysogeny decisions, but whether the mature communication peptide can be sensed directly by Bacillus subtilis and affect its...

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biorxiv.org/content/10.64898… Mo' evidence 'differential RNA decay' (term coined 2011 in doi:10.1128/AEM.05068-11 for MqsR), here, by toxin MazF, showing no cell death but instead a nice stationary-phase stress response.

Highly specific mRNA cleavage by the MazF endoribonuclease orchestrates stationary transcriptome...

Bacterial toxin-antitoxin (TA) systems are classically viewed as stress-activated toxic switches. Specifically, ribonucleolytic toxins are thought to indiscriminately cleave RNA to halt cellular...

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nature.com/articles/s41586-0… Truly excellent overview of phage defenses across kingdoms. Note the broad impact of toxin/antitoxin systems including those 'disguised 😉' ones (e.g., Metis, Paris, Panoptes, RAZR, and Clover).

Shared principles of human and bacterial antiviral immunity

Nature - The Review describes shared ancient, conserved mechanisms between human antiviral immunity and bacterial anti-phage systems, outlining universal principles of pathogen sensing, signalling...

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Two new type IX toxin/antitoxin systems for phage defense: (i) PanDA using c-di-AMP to repress a trans-membrane toxin (biorxiv.org/content/10.64898…) (ii) Panoptoo using c-UA/c-di-AMP to repress again a trans-membrane toxin (doi.org/10.64898/2026.08.10.…).

Minimal diadenylate cyclases have been co-opted to detect phage immune evasion

Many bacterial immune defenses transmit recognition of phage infection via the generation of diverse cyclic nucleotide second messengers. Phage have evolved to subvert this kind of immunity by...

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nature.com/articles/s41467-0… Excellent proof that phages induce the persister state (DOI 10.1111/1751-7915.14543) since phages try to prevent persistence by reducing ppGpp, the basis for persister cell formation by dimerizing ribosomes.

Phage portal proteins counteract stringent-response–mediated restriction

Nature Communications - Bacteria can protect themselves against viral infections by entering physiological states, such as the stringent response, that limit cellular resources. Here, the authors...

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Similar to the discovery that toxin/antitoxin systems stop phage ( journals.asm.org/doi/10.1128…) , then phage proteins like antitoxins were found to inhibit TA systems.

Exclusion of T4 phage by the hok/sok killer locus from plasmid R1 | Journal of Bacteriology

The hok (host killing) and sok (suppressor of killing) genes (hok/sok) efficiently maintain the low-copy-number plasmid R1. To investigate whether the hok/sok locus evolved as a phage-exclusion...

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science.org/doi/10.1126/scie… Interesting new type IX, anti-phage toxin/antitoxin system 'Metis' (although it is conveniently not called that) in which toxin MisA degrades NAD+ & antitoxin MisB degrades toxin-activating signal methylateddAMP nucleotides made by phage.

Bacteria sense virus-induced genome degradation via methylated mononucleotides

Phages often degrade the genome of their bacterial host to individual nucleotides. In this work, we describe Metis, a bacterial defense system that directly senses phage-mediated host genome degrad...

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biorxiv.org/content/10.64898… For 40 years it has been thought that the methanogen Methanosarcina acetivorans converts acetate only to methane. Instead, we demonstrate here 40% of the acetate is converted into ethanol.

Methanogenic Ethanol Production from Acetate

Biological ethanol production is important for the circular carbon economy and makes up 73% of the U.S. biological fuels market. Previously, we produced ethanol by reversing methanogenesis and...

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These new results (acetate to ethanol without cloning) are as surprising as those showing that methanogenesis can be reversed (doi.org/10.1038/s43247-026-0…) far more that the 'trace' levels originally reported.

Reversing methanogenesis to produce ethanol

Communications Earth & Environment - Acetate produced by methanogens from captured methane and carbon dioxide can be converted efficiently to ethanol, demonstrated by lab experiments on the...

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