Malcolm White

@mfwhite2.bsky.social

Molecular microbiologist at the University of St Andrews, Scotland. My scientific interests include: CRISPR, antiviral defence, cyclic nucleotide signalling, archaea, nucleases.

Loss of restriction-modification methyltransferases drives persistence to fluoroquinolones in Pseudomonas aeruginosa | bioRxiv

Loss of restriction-modification methyltransferases drives persistence to fluoroquinolones in Pseudomonas aeruginosa

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

biorxiv.org

Are you a motivated researcher interested in bacteria-host interactions? We have postdoc position available in my lab to join our Wellcome Trust funded collaborative team. We will study the role and regulation of the enigmatic sphingolipids in E. coli. Please share. www.jobs.ac.uk/job/DSX115/r...

Research Assistant/ Associate in Bacteria-Host Interactions at Newcastle University

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.

jobs.ac.uk

What a Friday, finally seeing this published in @cp-trendsmicrobiol.bsky.social! We hope this will be of interest to anyone working in the bacterial immune system field (or microbiology in general), and who wants an evolutionary take on it 🦠🧫 Open Access link: authors.elsevier.com/a/1nllx,L%7E...

Ellinor Alseth@ellinoralseth.bsky.social · 5mo ago

When is an antiphage mechanism an evolved defence adaptation? This question has been on my mind for so long, because despite the field’s rapid progress there is currently no widely agreed framework in place to answer it. So @brownlab.bsky.social and I wrote this, and I'm happy to share the preprint!

AlphaFold Server’s ligand menu just got a lot bigger and I almost missed it! You can now add any ligand from the wwPDB Chemical Component Dictionary. Just enter its CCD code 🥳

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The shared principles of human and bacterial antiviral immunity An honor to highlight remarkable discoveries from many labs over the past 12 years that unite previously disparate fields of how animal cells and prokaryotes defend against viruses. www.nature.com/articles/s41... rdcu.be/fzwyB

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 and effector...

nature.com