Fatemeh Askarian

Excited to share our new study published @pnas.org! We found that Shiga toxin-induced human cell death, long believed to be apoptosis, is in fact pyroptosis mediated by NLRP1 & gasdermin E. Congrats to all the authors! @uconnhealth.bsky.social @uconnresearch.bsky.social www.pnas.org/doi/10.1073/...

What is better than one? Two connected papers!

#NewResearch

S protein of Streptococcus pneumoniae activates PBP1a and coordinates with a wider GpsB-associated multi-protein complex to regulate peptidoglycan remodelling and cell division.

#MicroSky 🦠

www.nature.com/articles/s41...

Transcription co-inhibition alters drug resistance evolution and enhances Mycobacterium tuberculosis clearance from granulomas - Nature Microbiology Targeting two distinct steps of the transcription process yields synergistic antibiotics that kill non-replicating Mycobacterium tuberculosis and reduce drug resistance.

Superb work from labs of Elizabeth Campbell + Jeremy Rock @rockefeller.edu Nat Micro

By targeting distinct, functionally vulnerable steps of the transcription cycle, AAP-SO2 overcomes rifampicin resistance, suppresses resistance evolution, and synergistically enhances clearance of drug-tolerant Mtb

N-benzyl-N-methyldithiocarbamate (BMDC) combines with metals to produce antimicrobial and anti-biofilm activity against methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis | mSphere Antimicrobial-resistant bacteria, such as Staphylococcus aureus (MRSA) and Staphylococcus epidermidis, are a significant cause of morbidity and mortality in vulnerable populations, contributing to an escalating health and economic burden. Biofilms are an important reservoir that protects bacteria from immune clearance and antimicrobial agents. However, current strategies to effectively target MRSA biofilms are limited. This research describes a therapeutic approach that can disrupt biofilms in both MRSA and S. epidermidis, thereby enhancing bacterial clearance.

I am proud to share a new paper out of our lab. We showed that our antimicrobial works with copper and zinc to kill MRSA & Staph epi. It can function through mature biofilms they form and on multiple surfaces. This outstanding work was led by Yamil Sanchez-Rosario.

journals.asm.org/doi/10.1128/...

~1/3 of protein-coding genes are made in the secretory pathway. We curated >1000 of its machinery proteins, opening up new opportunities to engineer cells for drug production, to study cell-cell interactions, or modeling.
@cp-cellsystems.bsky.social paper -> authors.elsevier.com/a/1mFMc8YyDf...

Structure-guided design of a synthetic bile acid that inhibits Clostridioides difficile TcdB toxin - Nature Microbiology A bile acid-bound structure of toxin TcdB revealed the mechanism of inhibition and guided the design of a synthetic bile acid that alleviated Clostridioides difficile infection in mice.

#NewResearch

A bile acid-bound structure of toxin TcdB revealed the mechanism of inhibition and guided the design of a synthetic bile acid that alleviated Clostridioides difficile infection in mice.

#MicroSky 🦠

www.nature.com/articles/s41...

figure showing estimated proportion of cases in clusters, for each site. range from 0.04 to 0.93, mean estimate in random effects model is 0.57 [0.46,0.68]

#AMR #Klebsiella cause >100,000 neonatal deaths globally each year.

Our new preprint shows more than half of #Klebsiella pneumoniae neonatal sepsis cases in African and South Asian are nosocomial, acquired through transmission in neonatal units. #WAAW

doi.org/10.1101/2025...

#ToPrimeOrNotToPrime, this is the question! Excited for our new review @cp-trendsimmuno.bsky.social with @oceanedufies.bsky.social in which we discuss what is “priming” for the #NLRP3 #inflammasome & how we can harness this knowledge to better control human diseases! #InflammasomePower! #Free 👇👇👇

A host-directed adjuvant sensitizes intracellular bacterial persisters to antibiotics - Nature Microbiology The authors developed a screen to find compounds that modulate intracellular Staphylococcus aureus metabolism and discovered KL1, which sensitizes persisters to antibiotics by reversing host-induced tolerance.

Delighted to share our latest paper - A host-directed adjuvant sensitizes intracellular bacterial persisters to antibiotics. Excellently led by Dr. Kuan-Yi Lu. We think it's a great proof-of-concept that altering immune cell behavior can make antibiotics work better www.nature.com/articles/s41...

Chronic sensing of host-derived lipids is an all-in-one signal that primes and activates NLRP3. Activation of the NLRP3 inflammasome leads to the production of bioactive interleukin (IL)-1β fostering atherosclerosis. The current dogma is that NLRP3 must be first primed by microbial stimuli, know...

#InflammasomePower! 💥New paper alert💥 How is NLPR3 primed & activated in chronic non-communicable inflammatory diseases? With @oceanedufies.bsky.social &co we show that chronic exposure to oxPAPC drives NRF2 activation that primes & activates NLRP3 sustaining #atherosclerosis in mice & humans! 👇👇👇

Nasal microbionts differentially colonize and elicit cytokines in human nasal epithelial organoids | mSphere Human nasal microbiota often includes highly pathogenic members, many of which are antimicrobial resistance threats, e.g., methicillin-resistant Staphylococcus aureus and drug-resistant Streptococcus ...

Happy to share this new article online at #mSphere journals.asm.org/doi/10.1128/...
Human nasal organoids (HNOs) are a new model system for studying bacterial colonization and interspecies interactions. A big congratulations to the whole team, especially co-first authors: Andrea Boyd and Leah Kafer

Polymyxin B lethality requires energy-dependent outer membrane disruption - Nature Microbiology The antibiotic polymyxin B requires bacterial metabolic activity to cause sufficient damage to the outer membrane to access the inner membrane, which it permeabilizes via an energy-independent mechanism to kill the cell.

C̳H̳E̳C̳K̳ ̳I̳T̳ ̳O̳U̳T̳

Spectacular atomic force microscopy time course studies from Carolina Borrelli et al. in Nature Microbiology show how polymyxin drugs (like colistin) cause blebbing and shedding of the Gram-negative bacterial outer membrane

It looks almost like the bacilli 🦠 caught smallpox then died

Fermentative growth decreases the iron demand of Staphylococcus aureus Iron (Fe) is an essential nutrient for S. aureus survivability and pathogenesis, but excess Fe can catalyze the formation of toxic oxygen radicals, em…

Very happy to share some more good news. Our collaboration with Jeffrey Boyd's lab is now published at J Inorganic Biochemistry! Here, Jeff found that iron limitation reprograms S. aureus metabolism towards fermentation. We're grateful to be part of this study.

www.sciencedirect.com/science/arti...

Pleased to share the new article from UCSD Skaggs School of Pharmacy PharmD/PhD student Daniel Sun focused on repurposing FDA-approved agents to inhibit virulence, restore antibiotic susceptibility, bolster host defenses, and modulate inflammation v. S. aureus
www.annualreviews.org/content/jour...

Wall teichoic acid is required for DNA-triggered innate immune receptor activation by Staphylococcus aureus Receptors that stimulate inflammation are commonly activated by ligands that are buried within microbial cells. The mechanisms that facilitate immunostimulatory ligand release from microbes during inf...

Thrilled to share my work from the @jkagan1.bsky.social lab!

TLDR: O-acetylation and wall teichoic acid compete for space on S. aureus peptidoglycan. This competition regulates DNA release, and thus immune receptor activation, during infection!

www.biorxiv.org/content/10.1...

#microsky #immunosky

Staphylococcus aureus: a model for bacterial cell biology and pathogenesis | Journal of Bacteriology When talking about Staphylococcus aureus, one usually has in mind the diseases that can be caused by this bacterium, ranging from mild skin and soft tissue infections, such as abscesses and furuncles,...

"Among all bacterial species, S. aureus ranks second only to E. coli in the number of scientific publications."
It was a pleasure to contribute to this review, with @pinholab.bsky.social and Friedrich Götz
journals.asm.org/doi/10.1128/...

Cutting-edge tools for structural biology: bringing AlphaFold to the people The recent application of artificial intelligence-based prediction of protein and protein complex structures by AlphaFold has revolutionized biology. Here, we give an overview of the tools that make this revolution accessible to experimental microbiologists without training in bioinformatics or sophisticated computer equipment, and show how this helps to gain new insights.

Happy to share Christoph Elfmann's new paper that is now out in Trends in Microbiology! Discover tools to make the most out of AlphaFold and its iterations!
@c-elfmann.bsky.social @cp-trendsmicrobiol.bsky.social @unigoettingen.bsky.social @imprsgs.bsky.social #subtiwiki
www.cell.com/trends/micro...

"What makes S. aureus such a difficult vaccination candidate?" Here are some answers:

Myeloperoxidase transforms chromatin into neutrophil extracellular traps - Nature Myeloperoxidase, a highly expressed neutrophil protein, disassembles nucleosomes, facilitating neutrophil extracellular trap (NET) formation, and binds stably to NETs extracellularly.

📃 New paper alert!
The Zychlinsky Lab and @raunser-lab.bsky.social identified the first protein that converts chromatin into an immune effector: Myeloperoxidase transforms chromatin into neutrophil extracellular traps. Now published in @nature.com:
www.nature.com/articles/s41...

Abstract submissions are open for the Midwinter Conference of Immunologists @midwinter-immun.bsky.social!! www.midwconfimmunol.org The Early Bird Registration deadline is Nov 14, 2025.
There will be lots of Selected Abstract talks so submit an abstract to be considered!

Nasal Staphylococcus aureus carriage promotes depressive behaviour in mice via sex hormone degradation - Nature Microbiology Nasal colonization by Staphylococcus aureus is linked with depression in a human cohort and shown in a mouse model to cause decreased serotonin and dopamine in the brain.

#NewResearch

Nasal colonisation by S. aureus is linked with depression in a human cohort and shown in a mouse model to cause decreased serotonin and dopamine in the brain

#MicroSky #Depression

www.nature.com/articles/s41...

Commensal yeast promotes Salmonella Typhimurium virulence - Nature Commensal Candida albicans enhances the virulence and dissemination of Salmonella enterica subsp. enterica serovar Typhimurium.

Excited to share our new publication, out today in Nature! www.nature.com/articles/s41.... @kanchanj.bsky.social led this fascinating fungal-bacterial interaction project. We are grateful for our wonderful collaborators Brian Peters and David Underhill.

Epigenetic silencing of interleukin-10 by host-derived oxidized phospholipids supports a lethal inflammatory response to infections Phagocytes initiate immunity to invading microorganisms by detecting pathogen-associated molecular patterns via pattern recognition receptors. Pathoge…

💥 #ImmunometabolismPower! Excited to have this officially out @cp-immunity.bsky.social 💥 We show that pathogens induce the host to produce oxidized lipids which rewire the #metabolism of #macrophages, causing #epigenetic modifications which dampen anti-inflammatory IL-10, exacerbating #inflammation!

Looking for a new approach to studying or eliminating phages? Check out our study introducing anti-phage ASOs (antisense oligos) out in @Nature today. nature.com/articles/s4158…

Pleased to share and briefly highlight our new manuscript just published 𝘑𝘊𝘐 𝘐𝘯𝘴𝘪𝘨𝘩𝘵 (a short🧵)

"A STING-adjuvanted outer membrane vesicle nanoparticle vaccine protects against lethal 𝘗𝘴𝘦𝘶𝘥𝘰𝘮𝘰𝘯𝘢𝘴 𝘢𝘦𝘳𝘶𝘨𝘪𝘯𝘰𝘴𝘢 pneumonia"

🔗 doi.org/10.1172/jci....

In our new article, we show how P. aeruginosa, a major cause of chronic respiratory infections in #cysticfibrosis (CF), uses the Type VI Secretion System #T6SS and specific #toxins to eliminate competing bacteria
www.cell.com/cell-reports...
#cryoEM @dshatskiy.bsky.social @jakecolautti.bsky.social

Fishing out AIEC with FimH capturing microgels for inflammatory bowel disease treatment - Nature Communications Inflammatory bowel disease (IBD) is a chronic immune-mediated condition. This study presents a drug-free treatment strategy for IBD that targets bacterial adhesion, utilizing mannan oligosaccharide-lo...

New in Nat Comm

Pathogenic E. coli use protein FimH to grab onto the gut lining

New microgels mimic the mannose binding sites—acting as “decoys” to drag bacteria away and protect the intestine in IBD

Adherent-invasive E. coli (AIEC), enriched in Crohn’s disease, are a key target for this strategy

Staphylococcus aureus exploits lipoic acid salvage to combat host oxidative stress Acosta et al. find that ADP-ribosylation of the lipoic acid carrier protein GcvH-L promotes Staphylococcus aureus resistance to oxidative burst and facilitates infection. ADP-ribosylation leads to a s...

Happy to share Iván’s first-author pub from the lab! www.cell.com/cell-reports...

Type I CRISPR-Cas immunity primes type III spacer acquisition CRISPR-Cas systems are diverse, with microbes harboring multiple classes and subtypes. Type I DNA-targeting and type III RNA-targeting systems often c…

Ever wondered why some bacteria have multiple CRISPR-Cas systems? Our new study led by Leah Smith shows how type I CRISPR systems can promote the acquisition and retention of new spacers into a co-occuring type III system. www.sciencedirect.com/science/arti...

Who couldn’t use a little OUTSIDE ASSISTANCE 🦠 ???

Intracellular 𝘗𝘴𝘦𝘶𝘥𝘰𝘮𝘰𝘯𝘢𝘴 𝘢𝘦𝘳𝘶𝘨𝘪𝘯𝘰𝘴𝘢 cells can only escape vacuoles with help from extracellular cells via type III secretion–driven Ca²⁺ influx, ultimately promoting pathogen spread in vivo.

Suzanne Fleiszig Lab @UCBerkeley in Nature Comm