Nature Microbiology

Walk through our July issue! Read about: 💊Microbiome and AMR 🧊Permafrost microbes 🦠Phages and flagella ⚕️Cholera protection 💉Poxvirus vaccine design 🍄Commensal skin yeast and much more! nature.com/nmicrobiol/vol…

As permafrost thaws, microbes are constantly exchanging pieces of DNA. Research in @NatureMicrobiol suggests these genetic transfers help shape microbial communities and functions involved in carbon and nutrient cycling: spklr.io/6017EPuJB

New nucleases target modified DNA dlvr.it/TTWFzw #MicroSky

Very thankful to have this work out! We cultured small intestinal bacteria from children with environmental enteric dysfunction to understand their effects on post-natal growth and development. This allowed us to identify bacteria that contribute to the pathogenesis of EED.

Self-generated hydrogel ejects bacterial cells for localized biofilm dispersion dlvr.it/TTPRpl #MicroSky

Non-canonical gene amplifications facilitate adaptive evolution in bacteria dlvr.it/TTNGDb #MicroSky

Identification of genetic markers of quinine partial resistance in Plasmodium falciparum dlvr.it/TTNG53 #MicroSky

The penicillin-binding protein PBP1b fortifies the Escherichia coli division site against osmotic rupture dlvr.it/TTLL9B #MicroSky

Identification of chemical features for improved outer membrane permeation in mycobacteria using machine learning dlvr.it/TTHnx1 #MicroSky

Author Correction: Gut commensal Christensenella minuta modulates host metabolism via acylated secondary bile acids dlvr.it/TTGsmq #MicroSky

Epistatic interactions inform rational design of synthetic microbial communities for bioremediation dlvr.it/TTGMyT #MicroSky

Mobile genetic elements shape microbial diversity and functions in thawing permafrost soils dlvr.it/TTGMpt #MicroSky

END nucleases are antiphage defence systems targeting multiple phages with modified genomes dlvr.it/TTDw7p #MicroSky

Complex multicellularity is linked with expanded specialized metabolite production in microorganisms dlvr.it/TTDw5x #MicroSky

Bacteroides fragilis toxin promotes gall bladder cancer in mice dlvr.it/TTD3Ql #MicroSky

Voices of microbiome researchers in an artificial intelligence era dlvr.it/TTC70w #MicroSky

Addressing the zoonotic threat of merbecoviruses dlvr.it/TTC6z4 #MicroSky

Stuck on you Giardia dlvr.it/TTBCBn #MicroSky

Phages tame plant pathogens dlvr.it/TTBC9D #MicroSky

Thrilled to share that our paper, “Deep learning reveals antimicrobial peptides within prions,” is now published in @NatureMicrobiol @NaturePortfolio. In this work, we used AI to ask an unexpected question: could proteins best known for their role in fatal neurodegenerative diseases also encode molecules that fight infection? Prions and prion-like proteins are usually viewed through the lens of misfolding, aggregation, and disease. But biology is often more layered than our labels suggest. Our study shows that these proteins can contain encrypted antimicrobial peptides, which we call prionins. This connection did not come out of nowhere. Previous studies had shown that certain amyloid-associated protein sequences, including amyloid-β and the cellular prion protein, can have antimicrobial or host-protective activity. But until now, this had not been explored systematically across prion and prion-like proteins at scale. Using our deep-learning platform APEX 1.1, we screened 19.3 million peptide fragments from 2,897 prion-related proteins. This search identified 1,179 candidate antimicrobial peptides, moving from scattered observations to a global AI-guided search across millions of possible protein fragments. We then moved from prediction to experiment. Of 75 synthesized prionins, 59 inhibited at least one bacterial pathogen, including multidrug-resistant strains. Forty-two showed activity at 16 µM or lower against at least one pathogen. Many prionins disrupted bacterial membranes, and a subset showed encouraging early selectivity, including minimal hemolysis and limited cytotoxicity. Two lead prionins also reduced Acinetobacter baumannii burden in a mouse skin-infection model, with efficacy comparable to polymyxin B in the model tested. This is still early-stage work. We do not show that prionins are naturally released during infection or that they function physiologically in host defense, and these findings do not represent a treatment ready for patients. But the study raises a provocative idea: proteins long viewed mainly as biological “villains” may also encode useful molecular functions. More broadly, it shows how AI can become a discovery engine for biology: helping us search hidden molecular spaces, connect seemingly distant fields such as neurodegeneration and innate immunity, and uncover new starting points for medicine in places we might never have thought to look. At a time when new antibiotics are urgently needed, expanding where we search matters. Deeply grateful to @mdt_torres, Fangping Wan, and everyone who made this work possible, including @Penn, @CBE_Penn, @PennBioeng, @PennEngAI, @PennEngineers, @PennMedicine, @PennChemistry, @PennMicro, @PennPsych, and @PennSAS. nature.com/articles/s4156…