Rafal Mostowy

Rafal Mostowy

@rafalmostowy.bsky.social

Group leader at Jagiellonian University in Krakow, cofounder of Polonium Foundation. Working on evolution of sex in bugs.

609 followers136 following75 posts

Rafal Mostowy reposted

Marc Bonten
@marcbonten.bsky.social

Today, the E.mbrace study is published in #Lancet Infectious Diseases: a vaccine against infections by #Escherichia #coli failed. Study was similar to the CAPiTA study for a pneumococcal vaccine, only not for the outcome. Why? Read my substack: mbonten.substack.com/p/e-coli-is-... (1/)

mbonten.substack.comE. coli Is Not the PneumococcusToday, the results of the E.mbrace study were published: a vaccine against infections caused by Escherichia coli does not work.

Rafal Mostowy reposted

Vivek Mutalik
@vivekmutalik.bsky.social

Happy to share that @averynoonan.bsky.social paper “Phylogeny-agnostic strain-level prediction of phage–host interactions from genomes using machine learning” is now published in @natmicrobiol.nature.com 🎉🎊 👉🏽 rdcu.be/nR2NizD7H5va

Avery Noonan@averynoonan.bsky.social

We built GenoPHI: a machine learning workflow that predicts phage-host interactions at strain level. This could help rapidly select phages to treat drug-resistant bacterial infections or for microbiome engineering without exhaustive lab testing. www.biorxiv.org/content/10.1...

biorxiv.orgbiorxiv.org

Rafal Mostowy reposted

Leah Smith
@leahmsmith.bsky.social

Adapting the power of transposon sequencing to phages! Our final paper is out now👇 Our plasmids 🧬 are available on @addgene.bsky.social – try phage Tn-seq on your favorite phage!

Nature Microbiology@natmicrobiol.nature.com

Out Now! Defining the essential genome of diverse phages with phage Tn-seq #MicroSky

go.nature.comDefining the essential genome of diverse phages with phage Tn-seqNature Microbiology, Published online: 25 September 2026; doi:10.1038/s41564-026-02486-1Phage Tn-seq uses Tn5 transposon mutagenesis with anti-CRISPR-based selection and deep sequencing as a method to generate unbiased, genome-wide mutations across diverse phages

Rafal Mostowy reposted

Wytamma
@wytamma.bsky.social

One of the reasons I'm interested in local AI models is you're data can't be used for training - people say “I already put my data in onedrive so what's the difference to uploading it to an AI model?” Well one difference is that onedrive won't use your data to scoop you

Carl Zimmer@carlzimmer.com

Four days ago, a scientist was surprised by the news that Anthropic discovered new virus genes for making DNA. He says he’s been studying them for years—and feeding his data to Anthropic’s AI as part of his own research. Coincidence? Here’s my story. nyti.ms/3VSWayc

nyti.msDid Anthropic’s A.I. Really Make a Scientific Discovery on Its Own? (Gift Article)An expert at the University of Copenhagen said his team had been sharing its research with the company’s A.I. model, Claude, and that its new finding matched their work.

Rafal Mostowy reposted

Xavier Charpentier
@labxc.bsky.social

#microsky New preprint from the lab! Widespread immune systems protect bacteria against conjugative plasmids www.biorxiv.org/content/10.6... Kudos to the extremely talented lead author Ludovic Poiré! Key contributions by @francoisrousset.bsky.social and also help from C. Lesterlin/TacC lab. 🧵⬇️

biorxiv.orgWidespread immune systems protect bacteria against conjugative plasmidsConjugative plasmids are a class of mobile genetic elements capable of efficient transfer between bacterial cells. Although they can introduce beneficial traits such as antibiotic resistance to recipi...

Rafal Mostowy reposted

Conlon Lab
@bconlon.bsky.social

Loss of O-antigen due to wbbL mutations is common and associated with increased mortality in Escherichia coli bloodstream infections | Science Advances www.science.org/doi/10.1126/...

science.orgLoss of O-antigen due to wbbL mutations is common and associated with increased mortality in Escherichia coli bloodstream infectionsO-antigen loss in E. coli is not benign—wbbL mutations are associated with increased septic shock and higher mortality.
View full thread
View full thread
Rafal Mostowy
@rafalmostowy.bsky.social

RBPs showed remarkable levels of structural modularity. The most common type was N-terminal sharing, but other types were also observed (C-terminal sharing/variation, region conservation, recomb. hotspots). Many of these were relatively recent.

Rafal Mostowy
@rafalmostowy.bsky.social

Structurally different RBPs often share near-identical N-terminals. The most striking case: within Webervirus, near-identical genomes swap a depolymerase for an L-shaped tail fiber at a single locus — 85% N-terminal identity preserved, host-range changed.

Rafal Mostowy
@rafalmostowy.bsky.social

The dataset: 192 Klebsiella phages across 3 morphotypes — podoviruses, siphoviruses, myoviruses (incl. jumbophages) — spanning 96 capsule types, with halo phenotypes and empirical and genetic host-range all determined. The broadest K. pneumoniae phage collection studied structurally to date.

Rafal Mostowy
@rafalmostowy.bsky.social

We modelled all 382 RBPs with AlphaFold3 and resolved 39 structurally distinct classes — including 18 never described before — across all morphotypes. This is what the structural diversity of Klebsiella phage RBPs actually looks like.

Rafal Mostowy reposted

Piotr Rozwalak
@prozwalak.bsky.social

Mushuvirus is the most widespread phage genus in the human gut. 🌍 Together with other family members, these viruses occur in 89% of humans worldwide, including the Iceman Ötzi! How is it possible that they were hidden in previous metagenomic analyses? [1/7] Read: doi.org/10.64898/202...

Rafal Mostowy
@rafalmostowy.bsky.social

DepoCatalog maps the landscape of depolymerase diversity. What drives it — modularity, recombination, specificity switching — is exactly what we're working to uncover. More on this soon. 👀

Rafal Mostowy
@rafalmostowy.bsky.social

Polish phage science meets Polish visual storytelling 🇵🇱🦠 To celebrate our last paper, we collaborated with an artist who previously worked on The Witcher 3 — to create a comic about phages and why understanding them matters in the fight against antibiotic-resistant bacteria. Comic below 👇

Rafal Mostowy@rafalmostowy.bsky.social

🎉 New in @plosbiology.org: Temperate phages of Klebsiella pneumoniae show capsule-driven host tropism — but how? The working assumption was depolymerases: enzymes that chew through the bacterial sugar capsule. Turns out that's not the whole story. 🧵 journals.plos.org/plosbiology/...

View full thread
Rafal Mostowy
@rafalmostowy.bsky.social

Some GWAS hits pointed to completely uncharacterised RBPs with unknown folds — new biology waiting to be understood. Others resembled acetyltransferases, suggesting phages may actively add modifications to capsules, not just remove them. This suggests fascinating underlying evolutionary dynamics!

Rafal Mostowy
@rafalmostowy.bsky.social

The big picture: depolymerases recognise the sugar backbone; SGNH hydrolases recognise acetylation state. Two different keys for the same lock — and an ongoing molecular arms race over capsule chemistry with fascinating implications for prophage host dependence and evolution.

View full thread
Rafal Mostowy
@rafalmostowy.bsky.social

Both activity and specificity were hard to predict. Structurally related depos targeted different K-types. Divergent sequences sometimes converged on the same target. Even near-identical sequences could behave completely differently. The genotype-phenotype map of these enzymes is genuinely complex.

Rafal Mostowy
@rafalmostowy.bsky.social

The SGNH hydrolases: we produced two GWAS-predicted candidates and tested them. Both confirmed as active esterases — stripping O-acetyl groups from the capsule rather than degrading it. Not destroying the armour. Quietly removing its chemical decorations. A different mechanism entirely.

View full thread
Rafal Mostowy
@rafalmostowy.bsky.social

GWAS found predictors for 16/35 K-loci. Structural modelling revealed striking diversity: classical β-helix depolymerases yes — but also a major class of enzymes (SGNH hydrolases), novel RBPs and even acetyltransferases. The K-type associated toolkit is far broader than expected.

Rafal Mostowy
@rafalmostowy.bsky.social

We screened 50 candidates: 14 active, 34 did not express — and nothing in sequence, structure or genomic context predicted which ones would work. Of the 14 active, 5 targeted a different K-type than their host — consistent with capsule switching (Haudiquet et al., PLoS Biol 2021).

View full thread
Rafal Mostowy
@rafalmostowy.bsky.social

This raised 3 questions: ❓ What actually determines capsule tropism in prophages — are these really depolymerases? ❓ Why are depolymerases so hard to detect in prophage genomes — biology or annotation limits? ❓ When we do find candidates, are they even active?

Rafal Mostowy
@rafalmostowy.bsky.social

Two parallel approaches. GWAS on >2,500 Klebsiella genomes — no assumptions about protein function, just asking which prophage proteins associate with which capsule type. Independently: an experimental screen of recombinant candidate proteins tested against 118 K-types. Then we compared.

Rafal Mostowy
@rafalmostowy.bsky.social

Depolymerases match phages to specific capsules — different enzyme ↔ different sugar. But in prophages, they're surprisingly hard to find. A recent AI model by Concha-Eloko et al. tried to predict capsule specificity from prophage sequences, but struggled. We wanted to understand why.

Rafal Mostowy reposted

Peter Fineran
@peterfineran.bsky.social

Great fun presenting some of our research @otagomicroimmuno.bsky.social @universityofotago.bsky.social Including transposon mutagenesis of phages. www.biorxiv.org/content/10.6...

biorxiv.orgHigh-throughput transposon mutagenesis defines the essential genome of diverse phagesPhages are important drivers of bacterial evolution with therapeutic potential as antimicrobials. However, gaps in our understanding of phages and our inability to rapidly engineer them with new genetic cargo hinders progress towards phage-based therapies. To address the lack of unbiased, genome-wide mutational tools for phages, we developed transposon mutagenesis employing CRISPR-anti-CRISPR (Acr)-based selection and deep-sequencing (Phage Tn-seq). Transposon mutagenesis was effective for phages with unmodified or hypermodified genomes and a jumbo phage that protects its DNA within a nucleus. Phage Tn-seq enabled phage gene essentiality assignment consistent with structural proteomics and core gene conservation. Insertion biases allowed prediction of transcriptional direction and early injected phage DNA regions. We exploited the method to rapidly deliver new cargo to phage genomes in just a few days and used an AI-designed Acr to expand the phage transposon toolbox. Phage Tn-seq is a versatile tool to advance our understanding and applications of phages. ### Competing Interest Statement The authors have declared no competing interest. Royal Society Te Apārangi, https://ror.org/04tajb587 Alexander von Humboldt Foundation, https://ror.org/012kf4317 The L’Oréal Groupe Australia University of Otago, https://ror.org/01jmxt844
Asaf Levy@asaflevylab.bsky.social

Arabinose isn't only an inducer! @peterfineran.bsky.social gave a talk in our Hebrew Univ. microbiology journal club and mentioned his recent amazing finding that some phages add up to 3 arabinoses (!!) to their DNA to evade bacterial defense. Mahler et al. CHM 2025 www.cell.com/cell-host-mi...

Rafal Mostowy reposted

Mart Krupovic
@mkrupovic.bsky.social

With Eugene Koonin, we propose a concept of “the selfish ribosome”, under which evolution of life is viewed as a ribosomal takeover, where the ribosome evolved to consume most of the cell’s resources, while other cellular componentry ensures the propagation of the ribosome. arxiv.org/abs/2602.23268

Rafal Mostowy
@rafalmostowy.bsky.social

📢 Hiring a Postdoc in Computational Phage Biology (Kraków, Poland) We study the evolution & structural modularity of prophage-encoded glycan-degrading enzymes in Klebsiella pneumoniae — combining genomics and AlphaFold-based analyses. Details in attached PDF 👇

docs.google.comPostdoc AdPostdoctoral Position in Computational Phage Biology Microbial Genomics Group, Malopolska Centre of Biotechnology (MCB), Jagiellonian University, Kraków PL Summary We are seeking a postdoctoral rese...
Rafal Mostowy
@rafalmostowy.bsky.social

Looking for a strong computational biologist with experience in genomic/protein sequence analysis and a publication track record. Based at MCB (UJ), collaborating with Zuzanna Drulis-Kawa’s group (Wrocław). Informal enquiries very welcome.

Rafal Mostowy reposted

George Bouras
@gbouras13.bsky.social

Phold's manuscript is now available @narjournal.bsky.social thanks to @susiegriggo.bsky.social @npbhavya.bsky.social @vijinim.bsky.social @linsalrob.bsky.social @martinsteinegger.bsky.social @milot.bsky.social @eunbelivable.bsky.social & others not on bsky #phagesky academic.oup.com/nar/article/...

academic.oup.comProtein structure-informed bacteriophage genome annotation with PholdAbstract. Bacteriophage (phage) genome annotation is essential for understanding their functional potential and suitability for use as therapeutic agents.
George Bouras@gbouras13.bsky.social

Stoked to finally have a preprint out for Phold, our tool that uses protein structural information to enhance phage genome annotation #phagesky 1/n www.biorxiv.org/content/10.1...

biorxiv.orgProtein Structure Informed Bacteriophage Genome Annotation with PholdBacteriophage (phage) genome annotation is essential for understanding their functional potential and suitability for use as therapeutic agents. Here we introduce Phold, an annotation framework utilis...

Rafal Mostowy reposted

Beatriz Beamud
@beatrizbeamud.bsky.social

Can we exploit past phage infection events (prophages) to decipher the specificity of phage receptor-binding proteins such as depolymerases?🔎 Happy to share our recent work at @natcomms.nature.com 🔽 #microsky #phagesky www.nature.com/articles/s41...

nature.comUnlocking data in Klebsiella lysogens to predict capsular type-specificity of phage depolymerases - Nature CommunicationsHere, the authors exploit the genetic information encoded in Klebsiella prophages to model the interplay between bacteria, prophages, and their depolymerases, using a directed acyclic graph-model and a sequence clustering-based model.

Rafal Mostowy reposted

Rob Edwards
@linsalrob.bsky.social

🌟 Exciting news! We’re launching three fully-funded postdoc positions for "New Horizons for Synthetic Phages” Join us in tackling antimicrobial resistance with cutting-edge synthetic biology + AI bioinformatics. Based at Flinders Uni in vibrant Adelaide. 👇 Read on for details! #Phage