Jason Yang

I'm excited to share that we've received a NIBIB Trailblazer Award to advance our work on engineering therapeutic macrophages! Grateful for our team and excited to launch this collaboration with the Caleb @bashorlab.bsky.social at Rice!

Stressed bacteria develop antibiotic resistance more easily When bacteria are under energy stress – burning more energy than they produce, it increases their chances of developing antibiotic resistance. A new study offers new insight into how antibiotic...

Many thanks to ScienceNews.dk for highlighting our work!

Thank you @njmicrobe.bsky.social for this really nice writeup about our work!

Bioenergetic stress potentiates antimicrobial resistance and persistence - Nature Communications The bactericidal action of some antibiotics is associated with increased ATP consumption, cellular respiration, and reactive oxygen species formation. Here, Li et al. show that constitutive hydrolysis of ATP and NADH (or ‘bioenergetic stress’) potentiates the evolution of antibiotic resistance and persistence in E. coli.

A study in Nature Communications shows that constitutive hydrolysis of ATP and NADH, or ‘bioenergetic stress,’ potentiates the evolution of antibiotic resistance and persistence in E. coli. #medsky 🧪

Rutgers Health Research Identifies New Trigger Accelerating Antibiotic Resistance New Jersey Medical School study finds metabolic stress drives antibiotic tolerance and speeds resistance.

@rutgersu.bsky.social published a very nice article about our work!

www.rutgers.edu/news/rutgers...

@njms-mdphd.bsky.social

Many thanks to many members of the Yang Lab who contributed to this project (including many undergrads!) and to our collaborators Douglas McCloskey and Xiaoyang Su! 11/11

@njms-mdphd.bsky.social

We're eager to explore these topics in future projects and to see how generalizable these phenotypes are to pathogenic E coli and other species. We think these mechanisms may inform design of antibiotic adjuvants that can slow or prevent resistance development. 10/n

Importantly, little is known on how energy balance alters bacterial physiology. Although metabolic stress is known to inhibit growth and enhance metabolism, our work is the first to study stress responses and antibiotic phenotypes caused by disrupted energy balance. 9/n

By developing a new assay, Barry showed that mismatches between ATP utilization and production (disrupting ATP homeostasis) are sufficient for augmenting antibiotic killing. Thus, Barry's work introduces new concepts in understanding the interplay between energy balance and antibiotic efficacy. 8/n

Using bacterial genetics approaches, Barry was able to show that bioenergetic stress mechanistically induces stress responses that increase antibiotic stress-induced mutation rates and that protect against antibiotic killing. 7/n

This was also surprising that we previously showed that high levels of reactive oxygen species (ROS) were associated with high antibiotic killing, but the pF1 and pNOX cells had decreased killing while also possessing high levels of ROS! 6/n

Correlations between ATP availability and persistence are known and are usually thought about as correlations between metabolic activity (e.g., dormancy, low ATP) and killing efficacy. But Barry's cells have HIGH metabolic activity, which we previously found to INCREASE antibiotic killing. 5/n

Surprisingly, Barry found that bioenergetically stressed cells evolve antibiotic resistance FASTER than control cells (!!) and are also in general protected from bactericidal antibiotic stress (persistence). 4/n

These strains constitutively hydrolyze ATP (pF1) or NADH (pNOX), creating ATP or NADH sinks in these cells. These in turn induce 'bioenergetic stress' in which the cells are always struggling to meet their energetic demands. 3/n

Barry generated a genetic model system (frequently used by the metabolic engineering community) involving E coli cells over-expressing ATP synthase F1 complex genes (pF1) or heterologously expressing NADH oxidase from Streptococcus (pNOX). 2/n

Bioenergetic stress potentiates antimicrobial resistance and persistence - Nature Communications The bactericidal action of some antibiotics is associated with increased ATP consumption, cellular respiration, and reactive oxygen species formation. Here, Li et al. show that constitutive hydrolysis...

I'm thrilled to share the newest paper from the Yang Lab! Ever wonder how bacterial metabolism affects antibiotic resistance #AMR? In this study, Barry Li, a former MD/PhD student in the lab, took on this question using a systems and #synthetic_biology approach. 1/n

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

Honored to receive this year's Young Investigator Award from our local ASM branch!

Yang Lab had a terrific time at Rutgers' Biomedical Health Informatics and Artificial Intelligence Symposium yesterday. Great jobs by Yiqi Yan, Oliver Gu, and Reuven Rosen who presented on their work!

Our undergraduate machine learning maestro Edson Petry gave a terrific research presentation this afternoon at the Rutgers Pathways for Junior Scientists Research Program! #Rutgers #NJMS

Would you mind adding me too please? Thanks in advance!

I'm so proud of my technician Lia Goodwin who presented a poster at her first conference at the CSHL Systems Immunology meeting yesterday!

Terrific work by Ethan Bustad, Edson Petry, Oliver Gu, Braden Griebel, and Tige Rustad and wonderful support from our collaborator David Sherman (U Washington)! @rutgershealth.org 6/6

We are now using this work as a launching point for studying how individual (clinical) strains survive host and antibiotic stress and are eager to collaborate if you have some interesting phenotypes that you think are geneically regulated! 5/n

We found that transcription factor activities are better predictors of fitness under hypoxia than TF expression alone. Moreover, these analyses demonstrated that interpretable machine learning can reveal transcriptional programs causally regulating fitness under stress. 4/n

We performed gene regulatory network analyses to directly infer transcription factor activities from gene expression profiles. Using data from a TF over expression screen (TRIP), we trained an interpretable machine learning model that predicts Mtb fitness from RNA expression. 3/n

Pathogens live in hostile environments and must activate transcriptional stress response programs to survive exogenous stressors. In work led by Ethan Bustad, we sought to study Mtb fitness under hypoxic stress using systems biology approaches. 2/n

Frontiers | Predicting fitness in Mycobacterium tuberculosis with transcriptional regulatory network-informed interpretable machine learning

Ever wonder how Mycobacterium #tuberculosis deals with stressful environments? I'm pleased to share that in a second piece of good news this week, our recent work in collaboration with Shuyi Ma (Seattle Children's) was published at Frontiers in Tuberculosis. 1/n

www.frontiersin.org/journals/tub...

I am thrilled to share that our rock star MD/PhD student Barry Li successfully defended his PhD today entitled "Bioenergetic stress potentiates antimicrobial resistance evolution and persistence"! Barry is our first student to finish his PhD and I am so incredibly proud of him!

Microbiology and infectious diseases This page highlights recent articles on all aspects of bacteriology, mycology, parasitology and virology, covering the biology of pathogens, host-pathogen ...

Pleased to share our papers are highlighted by the editors at Nature Communications: www.nature.com/collections/...

👋 Can I please join also?