Snorre Sulheim

The metabolome of an E. coli CRISPRi library identifies benefits of minimal metabolite levels and targets for engineering Rapp et al. combine genome-scale CRISPRi and metabolomics in E. coli. CRISPRi of enzymes enforces metabolite accumulation, which leads to regulatory crosstalk and side reactions. This suggests that ma...

Cells maintain low metabolite pools to:
- enable substrate level regulation
- prevent competitive inhibition
- avoid side reactions

#microsky

www.cell.com/cell-systems...

Imbalance in gut microbial interactions as a marker of health and disease Imbalances in the human gut microbiome, or dysbioses, are associated with multiple diseases but remain poorly understood. Existing biomarkers of dysbiosis fail to capture the ecological mechanisms tha...

Imbalance in gut microbial interactions as a marker of health and disease www.science.org/doi/10.1126/...

Nice thread on the importance of spatial structure in microbial communities

Really elegant work showing how spatial distance can determine the net effect of two interaction mechanisms

#microsky

Metabolic blueprints of monocultures enable prediction and design of synthetic microbial consortia

A nice demonstration of how cross-feeding shapes small microbial community compositions

From Segré lab @dsegre.bsky.social

www.biorxiv.org/content/10.6...

A metabolic atlas of the Klebsiella pneumoniae species complex reveals lineage-specific metabolism and capacity for intra-species co-operation Why are there so many co-circulating Klebsiella pneumoniae clones? Using genomics and large-scale metabolic modelling of >7000 isolates, this study identifies structured, clone-specific metabolic spec...

Intra-species crossfeeding in K. pneumonia supports growth of co-cultivated partners. I think such commensal interactions are very common

journals.plos.org/plosbiology/...

Metabolic control of porin permeability influences antibiotic resistance in Escherichia coli - Nature Microbiology The permeability of bacterial porins is dynamically regulated by periplasmic proton and potassium concentrations, altering antibiotic resistance.

Metabolic control of porin permeability
www.nature.com/articles/s41...

Diagram illustrating "feed the enemy's enemy": ampicillin inhibits Pseudomonas aeruginosa. Citrobacter freundii acidifies the environment, further inhibiting P. aeruginosa.

New preprint from our lab www.biorxiv.org/content/10.1...! Andrea Dos Santos and Clément Vulin combine experiments and models showing how adding glucose can strengthen negative interactions between microbial species. This can be used in tandem with antibiotic treatment to inhibit pathogens!

This project wouldn't been possible without Peter Doubleday and @nzamboni.bsky.social at @imsb-eth.bsky.social. Peter conducted >10,000 mass spec analyses 🤯. So grateful for this opportunity to team up with the best of the best in metabolomics 😍

Read more: www.biorxiv.org/content/10.1...

#microsky

Note: Grab your laptop, the web app doesnt really work on your phone 🫤

Enabled by @lambdapp.bsky.social and Eric Ulrich 💪 and - as always - with strong support from @saramitri.bsky.social at @dmf-unil.bsky.social

Do you think transporters in E. coli contribute to metabolite release? No? Explore the effect of 66 different transporter knockout mutations on the exometabolome dynamics of ~300 metabolites yourself: keio.unil.ch

Teaser: Increased proline in ΔputP
#microsky #MEvoSky

After two rounds of "peer review" at Scientific reports 😵‍💫

Substrate utilization and cross-feeding synergistically determine microbiome resistance to pathogen invasion - Nature Ecology & Evolution Combining genome-scale metabolic modelling with in vitro and in planta experiments, the authors show that cross-feeding metabolites and substrate utilization synergistically determine microbial commun...

Great to see the increased use of genome-scale models in microbial ecology. Here is another recent example: www.nature.com/articles/s41...

But why is no one questioning the often implicit assumption that growth-optimization at the community level is the driving force of cross-feeding?

Great opportunity with a very nice PI👇

A beautiful review of the factors influencing spatial organization of microbiomes

An updated view of metabolic handoffs in microbiomes From the human gut to the deep ocean, diverse microbial communities underpin essential ecosystem processes. Limited understanding of the dynamics and interactions that shape these communities, however...

Nice review of metabolic exchanges in microbiomes across environments

www.cell.com/trends/micro...

Thanks Greg!

Wouldn't have happened without the support of @saramitri.bsky.social and crucial contributions from @juliensluneau.bsky.social @andrewhq9.bsky.social @pengellab.bsky.social + Gunn, Eric, Maggie and Alisson

Thanks to @snf-fns.ch and others for funding :)

These findings raise many new questions (to us) and has changed how we think about the emergence of cross-feeding interactions.

Metabolite release rates are sensitive to changes in intracellular metabolism, suggesting that metabolism is optimized on the network level to use, reuse and retain metabolites proportionally to their relative value. Retaining or reusing "cheap" metabolites might not be worth the investment.

Also, the value of a metabolite is more important than any other factor in explaining variability in release rates

Across the board we find such a correlation. The only real exception is an engineered strain.

Here we propose and test the hypothesis that metabolite release generally constitutes a fitness cost that microbes have evolved to reduce. If this is true -> release of high-value metabolites should be more strongly selected against compared to low-value metabolites

Microbes release lower-value metabolites at higher rates Microbes release a wide range of metabolites into their environment, yet the reasons for this release and the factors that influence release rates are not well understood. Here, using a combination of...

Excited to share the first results from my postdoc at @dmf-unil.bsky.social with @saramitri.bsky.social
www.biorxiv.org/content/10.1...