Yay!!!!! Awesome. Congratulations.

👏🥳 Congrats to Lucas Paoli and all authors for this collective effort, from data generation to analysis and discussion, and to the broader community whose tools, datasets, and ideas made this work possible (YAY iModulons).

Rather than a simple on/off response to infection, this work suggests that bacterial immunity is continuously tuned by environment, physiology, and genome organization!
Antiphage defenses form a regulated repertoire raising new questions about population-level immunity and single-cell heterogeneity.

Finally, we explore how expression differences are functionally relevant: by tuning conditions and strain background, we found conditions where famously repressed native E. coli CRISPR-Cas system becomes active.

What about the famous defense islands ?🛡️🏝️

They emerge as key regulatory units, frequently associated with candidates local transcription factors that could coordinate multiple systems.

How is transcription organized ?

Defense genes behave as cohesive transcriptional units, yet with notable internal asymmetries—often separating effectors from regulators, as exemplified in CRISPR-Cas or CBASS systems.

What could be the drivers of this variability ?

Antiphage system expression correlates with cellular physiology and mobile element activity, e.g. repression during SOS, association with IS activity.

This variability is not noise. Most systems show multi-fold expression changes across environmental (low or high temperatures🌡️), physiological (growth stage), or spatial gradients.

For examples, some systems seem expressed at the center of biofilms, others on the biofilm edges

What did we learn ?

Across species and strains, antiphage systems are typically moderately expressed, but expression is highly variable across conditions.

We put it in context with highly expressed genes (ribosomal proteins) or repressed ones (famous lac operon!).

To study this, we combine:
- ~10,000 public RNA-seq samples across 14 species
- a new, high-resolution dataset corresponding to 540 RNA seq samples: 15 E. coli strains, 6 environments, 2 growth stages, surveilling the expression of over 230 antiphage systems.

We love complex datasets ❤️💻

🐘In eukaryotes, immunity is largely switched on by infection.

🧫In bacteria, little is known, partly because much has been done outside native contexts. Given how fast phages act, many defenses may instead be tuned in advance by physiology and environment, rather than induced upon infection.