The resurgence of phage therapy has renewed interest in the interplay between phage resistance and antibiotic susceptibility and has stimulated research in the emergent field of non-canonical cellular functions carried out by defence systems. Yet it remains largely unknown whether intracellular antiphage defence systems influence bacterial physiology, resistance or persistence to antibiotics. Here we discovered that besides its canonical antiphage defence function, the type I restriction modification (RM) system profoundly affects the physiology of the opportunistic pathogen Pseudomonas aeruginosa. Deletion of the type I RM methyltransferase HsdM reduces the size of the bacterial nucleoid and delays DNA replication initiation and exit from lag phase in P. aeruginosa PAO1. Crucially, P. aeruginosa strains isolated from patients with cystic fibrosis (CF) and lacking the RM type I system also display slower growth compared to strains isolated from other sites of infections and encoding this system. Deletion of HsdM selectively increases the levels of persisters that survive treatment with fluoroquinolones by displaying enhanced SOS response but without acquiring resistance. Importantly, we measured elevated persistence to fluoroquinolones also in P. aeruginosa CF isolates lacking the type I RM system, providing a functional link between RM systems, slow growth and persistence to fluoroquinolones. Together these findings open a new way of approaching bacterial susceptibility to antibiotics, bringing antiphage defence systems in a forward-facing position in this field. ### Competing Interest Statement The authors have declared no competing interest. Biotechnology and Biological Sciences Research Council, BB/V008021/1, BB/X003051/1 Engineering and Physical Sciences Research Council, EP/Y023528/1 Medical Research Council, MR/Y033892/1 Novo Nordisk Foundation, NNF 18OC0033946 Deutsche Forschungsgemeinschaft, 390874280

Nature Microbiology, Published online: 25 September 2026; doi:10.1038/s41564-026-02455-8HIDEN-SEQ (hidden Acr-enabled transposon-insertion sequencing) is a transposon-insertion sequencing method for phages that systematically links their genes to selectable phenotypes.

Bacterial defence systems are diverse and form major barriers to horizontal gene transfer and bacteriophage (phage) infection. Though restriction-modification systems were the first such defences disc...

Cultured phage collections provide essential access to viral biology, but they capture only a small and biased fraction of natural phage diversity. Key barriers to diverse phage isolation are likely t...

New report shows key indicators of Earth’s health are ‘outside the safe operating space’ as climate disaster looms

US president on Truth Social claims his new plan for the 250ft arch comes at the ‘strong request’ of the US military

Explore an exciting academic career as a Research Assistant/ Associate in Bacteria-Host Interactions. Don't miss out on other academic jobs. Click to apply and explore more opportunities.

Hazel O'Connor - Eighth Day 1980 Check Out Hazel O'Connor - Eighth Day (Unknown Version - Video) https://www.youtube.com/watch?v=Pe9EYV6SJR8 Copyright Disclaimer: Under Section 107 of the Copyright Act 1976, allowance is made for "fair use" for purposes such as criticism, comment, news reporting, teaching, scholarship, and research. Fair use is a use permitted by copyright statute that might otherwise be infringing. Non-profit, educational or personal use tips the balance in favor of fair use.

Bacteria use nucleotide second messengers to couple phage recognition to antiviral effector activation. Here, we identify Pucsar, an ofshoot of the Pycsar-related antiphage family, whose cyclases gene...

Diverse E. coli phage genomes have hypermutable DNA regions that promote reversible frameshift mutations through DNA polymerase slippage, generating population heterogeneity that enables host exploita...

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

Phages are the naturally occurring viruses of bacteria (see Table 1 for key definitions). They have co-evolved with their bacterial prey across billions of years, resulting in highly specific phage-ho...

Writer Sarah Wilson argues we’re hurtling toward the same end as ancient Rome and the Mayan civilisation – but there’s plenty to fight for

Systematic analysis of prokaryotic STAND NTPases — relatives of animal and plant immune receptors — uncovers diverse antiviral sensors that detect most of the core structural and replicative proteins of bacteriophages.

The phage-encoded protein PptA enables its DNA to masquerade as the host and evade cleavage, providing a potential foundation for engineering therapeutic phages that could bypass this widespread defence system.

Here’s a more natural, flowing version of that section..."

CRISPR–Cas systems transcriptionally tune diverse innate defences using CRISPR RNA-like guides to balance antiviral protection with fitness, and hyperactivate these defences when compromised, establis...

Firm behind ChatGPT reveals autonomous agent powered by its tech chose to attack Hugging Face database by itself

All organisms defend against viral infections through active immunity mechanisms that clear the virus or population-level mechanisms that cause regulated cell death. Recent research increasingly shows...

Shomar, Guillaume, et al. report the genomics-driven discovery of a family of more than 2,000 lanthipeptide biosynthetic gene clusters with anti-phage potential. They experimentally demonstrate anti-p...

YprA-family helicases represent a key hub in the prokaryotic defense network. Through phylogenetic analysis of YprA, Bell and colleagues identify a distinct class of defense systems, called ARMADA. AR...

Nature Microbiology, Published online: 26 June 2026; doi:10.1038/s41564-026-02407-2The END nuclease targets eight phage families with at least ten different known DNA modifications, but not unmodified DNA. Its specificity is dictated by the C-terminal iEndoIII domain. To combat END, modified phages encode direct-binding inhibitors.