Michael Shiloh, MD, PhD

Congrats @samuelalvarez.bsky.social and the entire team on this work characterizing established (i.e. M cells) and new cells in the mucosal immune system! The new cells we named WISP cells as they are found in both adenoid and tonsils. Read the paper to find out so much more!

A Diagnostic Stewardship Success: Implementing a Urine Culture Reflex Policy in the Emergency Department of a Large Safety-Net Hospital AbstractBackground. Urinalyses and urine cultures (UCs) are frequently ordered simultaneously in emergency departments (EDs) to increase efficiency and dec

Similar to this study.
academic.oup.com/ofid/article...

Quantifying Dissemination of Antibiotic Resistance Genes in Air from a Dairy Farm and Swine Farm Farms are a suspected source of dissemination of antibiotic resistance genes (ARGs) to the atmosphere, but their contribution remains poorly quantified. This study investigated the concentrations, emi...

Quantifying Dissemination of Antibiotic Resistance Genes in Air from a Dairy Farm and Swine Farm, led by PhD student David Kormos, now published! We found ARGs in a range of particle sizes, indicating potential for inhalation exposure and long-range transport.

pubs.acs.org/doi/10.1021/...

Mycobacterium tuberculosis sulfolipid-1 (Sl-1) increases the excitability of mouse and human TRPV1-positive sensory neurons in a YM254890-reversible fashion Cough is a hallmark sign of tuberculosis and key driver of transmission. While traditionally attributed to host-driven inflammation, we previously demonstrated that Mycobacterium tuberculosis lipid ex...

Congrats to Dhananjay Naik from @tedpricethepainguy.bsky.social's lab at UT Dallas on their new preprint deeply characterizing the nociceptive activity of SL-1 on mouse & human neurons.
www.biorxiv.org/content/10.1...

Enjoyed celebrating John Neff’s PhD graduation ceremony yesterday.

I get the cartoonist's point, but, if I'm going to be pedantic (and scientifically accurate), since measles is an airborne disease with the highest transmissibility of all pathogens, the girl on the left would have been exposed/infected in the top left panel.

I wish I could find it online, but 30 years ago my PhD advisor had a cartoon on his door (maybe New Yorker?), with 3 spinning-wheels. On one was "eggs, butter, fat, sugar, coffee, etc.", then "causes, cures, etc." and the last "cancer, heart disease, stroke, etc." So, I think the answer is "yes".

Thank you Olivier!

Thank you Kat!

Ted Lasso Thank You GIF - Ted lasso Thank you Mercy buckets - Discover & Share GIFs Click to view the GIF

This project would not have been possible without the financial support of @niaidnews.bsky.social ws.bsky.social, @bwfund.bsky.social nd.bsky.social, and @thewelchfoundation.bsky.social. 14/14
tenor.com/view/ted-las...

All credit belongs to Kubra Naqvi, PhD (not yet on Bluesky), who led this project from the start. We are also indebted to our chemistry collaborators at @unileiden.bsky.social and neuroscience collaborators @utdpaincenter.bsky.social. 13/14

Mycobacterial Phenolic Glycolipid Triggers ATP-Mediated Neuronal P2X3 Signaling and Cough Cough drives respiratory pathogen transmission, yet how microbes directly engage host sensory neurons to trigger cough is largely unknown. We previously demonstrated that the Mycobacterium tuberculosi...

Please check out and share our preprint relating to the aerobiology of one of the most successful human pathogens, Mtb. 12/14 @idsainfo.bsky.social sky.social @utswinfdis.bsky.social is.bsky.social @carlzimmer.com
#InfectiousDisease #Purinergic #DrugDiscovery
www.biorxiv.org/content/10.1...

We propose that Mtb evolved to produce multiple neuron activating molecules to co-opt the host cough reflex, thus facilitating its own spread from person to person. Therapeutically, P2X3 antagonists may help reduce airborne transmission of Mtb. 11/14

An image showing the role of ATP in neuronal activation

PGL triggers rapid extracellular ATP release from host cells through pannexin channels. ATP then binds neuronal P2X3 purinergic receptors. Blocking P2X3 with a specific antagonist inhibits PGL-mediated neuronal activity. ⚠️. #anti-tussive 10/14

A picture of animals and their mycobacterial hosts

PGL is also made by other mycobacteria, like M. bovis, M. leprae, M. marinum and M. kansasii. By organically synthesizing PGL analogs, we found that neuroactivity is proportional to saccharide chain length & structure. Mtb PGL triggers the most robust activity with the lowest EC50, 30 pM! 9/14

Balthazar Ko GIF - Balthazar Ko Combat - Discover & Share GIFs Click to view the GIF

Combining PGL + SL-1 ➡️ super-activation of neurons. This suggests that Mtb HN878 uses a “one-two punch” to maximize cough and transmission. 8/14
tenor.com/view/balthaz...

An image of a guinea pig being exposed to PGL

We used whole body plethysmography in guinea pigs (the best model of human cough reflexes) to show that PGL is sufficient to induce cough 🚀. #cough #plethysmography #physiology 7/14

An image of human dorsal root ganglia being used in patch clamp experiments.

Together with @tedpricethepainguy.bsky.social’s lab at @utdpaincenter.bsky.social, we also found through single cell recording in human nociceptive neurons that PGL treatment raises the resting membrane potential, thereby increasing excitability. #electrophysiology 6/14

We used live cell calcium imaging in mouse and human nociceptive neurons to show that PGL alone → robust neuronal firing. Shown here a representative live cell calcium imaging experiment with a nociceptive neuronal cell line. Cells become green once activated → increased intracellular calcium. 5/14

Mtb HN878 is an isolate of the Mtb lineage 2, which some studies how shown is more transmissible than other Mtb lineages. Intriguingly, the commonly-studied lineage 4 strains have a frameshift mutation in a key polyketide synthase, rendering them unable to make PGL. #Aerobiology #Evolution 4/14

Mycobacterial Phenolic Glycolipid Triggers ATP-Mediated Neuronal P2X3 Signaling and Cough Cough drives respiratory pathogen transmission, yet how microbes directly engage host sensory neurons to trigger cough is largely unknown. We previously demonstrated that the Mycobacterium tuberculosi...

👉 Today: we reveal in a preprint on @biorxivpreprint.bsky.social that phenolic glycolipid (PGL), produced by the hyper-transmissible HN878 strain, is a second glycolipid neuronal activator. #glycobiology 3/14
www.biorxiv.org/content/10.1...

Mycobacterium tuberculosis Sulfolipid-1 Activates Nociceptive Neurons and Induces Cough - PubMed Pulmonary tuberculosis, a disease caused by Mycobacterium tuberculosis (Mtb), manifests with a persistent cough as both a primary symptom and mechanism of transmission. The cough reflex can be trigger...

In 2020 we showed that the Mtb glycolipid sulfolipid-1 (SL-1) can directly activate lung-innervating neurons and trigger cough. But is that the whole story? 🧐 2/14
pubmed.ncbi.nlm.nih.gov/32142653/

YouTube video by Massachusetts Institute of Technology (MIT) Coughs and sneezes travel farther than you think

🦠💨 Why do some TB strains make you cough more? Cough isn’t just an annoying sign and symptom of active tuberculosis - it’s one way that Mycobacterium tuberculosis spreads from person to person. 1/14
#Tuberculosis #CoughScience #Aerobiology #Neuroimmunology #Microbiology youtu.be/9qqHOKUXY5U?...

And stay tuned for several papers outlining his results using ABPP to generate a map of reactive cysteines during macrophage infection with bacterial pathogens.

Celebrating the next PhD to leave the lab. Congratulations Dr. Neff. As per Shiloh lab tradition, John’s graduation cake represents Activity Based Proteomic Profiling with rock candy “proteins”.

Right…. It would be really sad if on one of his last minute slides something happened and then the Eagles beat Carson Wentz….

Two years ago they dominated for three quarters and were one dubious “Mahomes special” holding call from possibly winning the game. Eagles have a much stronger roster this time around. Chiefs have Mahomes, Reid and the refs. Other than that, Eagles are a superior team.

Sorry for your loss. You know there’s an amazing football team with a pretty cool owner who supports autism research and doesn’t care about publicity. Oddly enough, that team will be playing next Sunday 😆

Michael Oliver needs to be investigated for corruption. This is not a joke.

Scientists and Physicians

I’m being serious here —at this precarious juncture, along with all other defensive and support strategies, it is important to seize the public narrative—high level investment and leadership in medical discovery and innovation is unabashedly patriotic!

USA! USA! USA!