Jake Choby

I’m excited to share the final two papers from my postdoc with @dweisslab.bsky.social. Together, they reveal two mechanisms of antibiotic heteroresistance (HR) that do not rely on gene copy-number changes, but instead arise from cell-to-cell differences in transcription. A short thread: 1/4

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science.orgCombinatorial action of regulatory systems generates colistin heteroresistanceThe mechanism by which phenotypic heterogeneity is generated within a bacterial population and leads to colistin heteroresistance has been unclear. Heteroresistance is a form of antibiotic resistance ...

2. In another Enterobacter isolate, ~1% of cells had preexisting σE activity—and only those cells survived colistin. σE generated bimodality, while PhoPQ generated resistance: two distinct regulatory systems acting together to produce heterogeneity in resistance. www.science.org/doi/10.1126/... 3/4

Together, these studies show that HR can arise without gene amplification. Transcriptional states shaped by the environment or regulatory networks can determine which cells survive. Grateful to our collaborators: @tozturk90.bsky.social, @ernstlab.bsky.social, and @victorband.bsky.social +others! 4/4

nature.comHeterogeneity in the response to the metabolic environment drives fosfomycin heteroresistance - Nature CommunicationsChoby et al. show an antibiotic-resistant subpopulation is generated by heterogeneity in expression of an antibiotic importer repressed by environmental glucose, suggesting diabetes-related infection ...

1. In an Enterobacter isolate, variation in GlpT expression generated the fosfomycin-resistant subpopulation, with FosA enhancing resistance. Glucose increased HR, including in diabetic models, showing the host environment can shape resistance. @natcomms.nature.com www.nature.com/articles/s41... 2/4

Jake Choby reposted

Nature Communications

@natcomms.nature.com

28 Aug

#Bacteria Ornithine utilization is important for Acinetobacter baumannii during gut colonization. A protein that regulates ornithine catabolism helps the pathogen to sense and respond to competition for amino acids with the resident microbiota @xiaomeiren.bsky.social @laurenpalmer.bsky.social

dlvr.itA regulator of amino acid catabolism controls Acinetobacter baumannii gut colonization - Nature CommunicationsAsymptomatic gut colonization is a reservoir for antimicrobial resistance (AMR) such as by the bacterium Acinetobacter baumannii. Geary and Ren, et al., report that A. baumannii evolved a regulator that helps sense competition from the gut microbiota.

Jake Choby reposted

Erin Green

@erinrgreen.bsky.social

29 Apr

Excited to share the final part of my postdoc work, where we investigate the impact of antimicrobial treatment on susceptibility to hospital-acquired Acinetobacter baumannii pneumonia. Thanks to our amazing group of collaborators for their contributions to this study! www.pnas.org/doi/10.1073/...

pnas.orgThe intestinal microbiota impacts nutritional immunity and resistance to Acinetobacter baumannii pneumonia | PNASBroad-spectrum antibiotics are frequently administered to intensive care unit patients as part of empiric care. This treatment has been associated ...

Jake Choby reposted

David Weiss

@dweisslab.bsky.social

12 Mar

Bacteria in our BRAINS??! We observed translocation of bacteria from the gut to the brain via the vagus nerve. This occurred after high fat diet, or without dietary changes in mouse models of Alzheimer’s, Parkinson’s, and autism. journals.plos.org/plosbiology/...

journals.plos.orgTranslocation of bacteria from the gut to the brain in miceRecent studies link gut dysbiosis to neurological disease, but the underlying mechanisms remain unclear. This study shows that a high-fat diet increases gut permeability and enables bacterial transloc...

Jake Choby reposted

AMR-kleb/staph

@s-rowe-conlon.bsky.social

1 Dec 2025

Thrilled to share our latest paper on antibiotic treatment failure of Klebsiella pneumoniae liver abscesses www.pnas.org/doi/full/10.... @drwalkermsbanta.bsky.social

pnas.orgAntibiotics accumulate in Klebsiella pneumoniae liver abscesses but fail to eliminate antibiotic-tolerant populations | PNASLiver abscesses caused by hypervirulent Klebsiella pneumoniae (hvKp) can lead to severe metastatic complications, with mortality rates ranging from...

Jake Choby reposted

Conlon Lab

@bconlon.bsky.social

10 Oct 2025

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...

nature.comA host-directed adjuvant sensitizes intracellular bacterial persisters to antibiotics - Nature MicrobiologyThe 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.

Jake Choby reposted

Lauren Palmer

@laurenpalmer.bsky.social

4 Aug 2025

Super excited to share our paper online 🚨today🚨 in Cell Host & Microbe‬! Xiaomei Ren @xiaomeiren.bsky.social and Mason Clark @rmasonclark.bsky.social‬ co-led discovery of ecological factors for Acinetobacter baumannii carriage in the gut, a reservoir for pathogen spread. 🎉 tinyurl.com/443kfefk

Cell Host & Microbe@cp-cellhostmicrobe.bsky.social

Amino acid competition shapes A. baumannii gut carriage Acinetobacter baumannii uses ornithine to compete w/ microbiota & persist in gut. Amino acid supplementation & differences in diet promote A. baumannii gut colonization in mice & humans @laurenpalmer.bsky.social‬ www.cell.com/cell-host-mi...

cell.comAmino acid competition shapes Acinetobacter baumannii gut carriageRen and Clark et al. show that Acinetobacter baumannii uses ornithine to compete with the resident microbiota and persist in the gut. Additional evidence demonstrates that amino acid supplementation a...

rdcu.beCopy number flexibility facilitates heteroresistance to increasing antibiotic pressure and threatens the beta-lactam pipelineNature Communications - Choby et al. show that dynamic increases in the copy number of preexisting β-lactamase genes in heteroresistance enables resistance of continua of cellular...

2 July 2025

Excited to share the work with @dweisslab.bsky.social‬ and great collaborators on how gene amplification generates dynamic heteroresistance to new beta-lactams, like cefiderocol. We hope drug developers will consider heteroresistance during antibiotic development rdcu.be/euijW

2 July 2025

It's a good time to mention that I’ve just started as an assistant professor at the University of North Carolina SOM, Micro & Immuno, where we will work to understand mechanisms that generate heteroresistance and phenotypic heterogeneity in Enterobacter and other multi-drug resistant Gram- pathogens

@francoismayer.bsky.social

2 July 2025

Thanks to my colleagues, friends, and especially mentors @dweisslab.bsky.social and Eric Skaar for guidance along the way

Jake Choby reposted

François Mayer

6 Jan 2025

News & Views 📄 - Zinc-dependent β-lactam resistance at a cost By Jacob Choby & David Weiss www.nature.com/articles/s41...

nature.comZinc-dependent β-lactam resistance at a cost - Nature MicrobiologyChemical genomics reveals the fitness cost of bacterial metallo-β-lactamase in zinc-deplete environments, with implications for treatment options.