Julian Trouillon

Last Name

Trouillon

First Name

Julian

ORCID

0000-0003-1675-0896

Organisational unit

03713 - Sauer, Uwe / Sauer, Uwe

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Publications 1 - 8 of 8

Degradation of extracellular polymeric substances shapes microbial community diversity
Pontrelli, Sammy; Bigovic Villi, Kian; Sichert, Andreas; et al. (2025)
PLoS Biology
Metabolic cross-feeding networks are central to shaping microbial community dynamics in environments ranging from the rhizosphere, gut, and marine carbon cycling. Yet cross-feeding has predominantly been viewed by examining exchanged small metabolites. In contrast, the role of extracellular polymeric substance (EPS)—a complex mixture of proteins, polysaccharides, DNA, and humic-like compounds—in cross-feeding remains poorly understood, mainly due to technical challenges in measuring their secretion relative to small metabolites. Using chitin-degrading microbes as a model system, we used a bicarbonate-buffered bioreactor coupled with elemental analysis, which allowed us to quantify both EPS and small metabolite secretion. This revealed that ~25% of carbon exuded by a chitin degrader is in the form of EPS. EPS was produced at similar levels across marine chitin-degrading isolates and seawater communities, underscoring its importance relative to small metabolites. Notably, different sources of EPS were found to select for distinct and diverse microbial communities. Combining in vitro enzyme assays and untargeted metabolomics, we show that EPS undergoes sequential degradation—from large oligomers to smaller, broadly accessible monomers. This sequential breakdown creates a temporal succession of metabolic niches, potentially fueling a shift from specialist species degrading complex substrates to a more diverse community of generalists using simpler monomers. By identifying EPS as a major and dynamic contributor to cross-feeding networks, our findings reveal a hidden layer of complexity in how microbial communities assemble and function across ecosystems.
Metabolomics and Microbial Metabolism: Toward a Systematic Understanding
Holbrook-Smith, Duncan; Trouillon, Julian; Sauer, Uwe (2024)
Annual Review of Biophysics
Over the past decades, our understanding of microbial metabolism has increased dramatically. Metabolomics, a family of techniques that are used to measure the quantities of small molecules in biological samples, has been central to these efforts. Advances in analytical chemistry have made it possible to measure the relative and absolute concentrations of more and more compounds with increasing levels of certainty. In this review, we highlight how metabolomics has contributed to understanding microbial metabolism and in what ways it can still be deployed to expand our systematic understanding of metabolism. To that end, we explain how metabolomics was used to (a) characterize network topologies of metabolism and its regulation networks, (b) elucidate the control of metabolic function, and (c) understand the molecular basis of higher-order phenomena. We also discuss areas of inquiry where technological advances should continue to increase the impact of metabolomics, as well as areas where our understanding is bottlenecked by other factors such as the availability of statistical and modeling frameworks that can extract biological meaning from metabolomics data.
Genomic footprinting uncovers global transcription factor responses to amino acids in Escherichia coli
Trouillon, Julian; Doubleday, Peter F.; Sauer, Uwe (2023)
Cell Systems
Our knowledge of transcriptional responses to changes in nutrient availability comes primarily from few well-studied transcription factors (TFs), often lacking an unbiased genome-wide perspective. Leveraging recent advances allowing bacterial genomic footprinting, we comprehensively mapped the genome-wide regulatory responses of Escherichia coli to exogenous leucine, methionine, alanine, and lysine. The global TF Lrp was found to individually sense three amino acids and mount three different target gene responses. Overall, 531 genes had altered RNA polymerase occupancy, and 32 TFs responded directly or indirectly to the presence of amino acids, including regulators of membrane and osmotic pressure homeostasis. About 70% of the detected TF-DNA interactions had not been reported before. We thus identified 682 previously unknown TF-binding locations, for a subset of which the involved TFs were identified by affinity purification. This comprehensive map of amino acid regulation illustrates the incompleteness of the known transcriptional regulation network, even in E. coli.
The core and accessory Hfq interactomes across Pseudomonas aeruginosa lineages
Trouillon, Julian; Han, Kook; Attrée, Ina; et al. (2022)
Nature Communications
The major RNA-binding protein Hfq interacts with mRNAs, either alone or together with regulatory small noncoding RNAs (sRNAs), affecting mRNA translation and degradation in bacteria. However, studies tend to focus on single reference strains and assume that the findings may apply to the entire species, despite the important intra-species genetic diversity known to exist. Here, we use RIP-seq to identify Hfq-interacting RNAs in three strains representing the major phylogenetic lineages of Pseudomonas aeruginosa. We find that most interactions are in fact not conserved among the different strains. We identify growth phase-specific and strain-specific Hfq targets, including previously undescribed sRNAs. Strain-specific interactions are due to different accessory gene sets, RNA abundances, or potential context- or sequence- dependent regulatory mechanisms. The accessory Hfq interactome includes most mRNAs encoding Type III Secretion System (T3SS) components and secreted toxins in two strains, as well as a cluster of CRISPR guide RNAs in one strain. Conserved Hfq targets include the global virulence regulator Vfr and metabolic pathways involved in the transition from fast to slow growth. Furthermore, we use rGRIL-seq to show that RhlS, a quorum sensing sRNA, activates Vfr translation, thus revealing a link between quorum sensing and virulence regulation. Overall, our work highlights the important intra-species diversity in post-transcriptional regulatory networks in Pseudomonas aeruginosa.
Metabolic landscape of the male mouse gut identifies different niches determined by microbial activities
Meier, Karin H.U.; Trouillon, Julian; Li, Hai; et al. (2023)
Nature Metabolism
Distinct niches of the mammalian gut are populated by diverse microbiota, but the contribution of spatial variation to intestinal metabolism remains unclear. Here we present a map of the longitudinal metabolome along the gut of healthy colonized and germ-free male mice. With this map, we reveal a general shift from amino acids in the small intestine to organic acids, vitamins and nucleotides in the large intestine. We compare the metabolic landscapes in colonized versus germ-free mice to disentangle the origin of many metabolites in different niches, which in some cases allows us to infer the underlying processes or identify the producing species. Beyond the known impact of diet on the small intestinal metabolic niche, distinct spatial patterns suggest specific microbial influence on the metabolome in the small intestine. Thus, we present a map of intestinal metabolism and identify metabolite-microbe associations, which provide a basis to connect the spatial occurrence of bioactive compounds to host or microorganism metabolism.
Functional and Pangenomic Exploration of Roc Two-Component Regulatory Systems Identifies Novel Players Across Pseudomonas Species
Simon, Victor; Trouillon, Julian; Attrée, Ina; et al. (2025)
Molecular Microbiology
The opportunistic pathogen Pseudomonas aeruginosa relies on a large collection of two-component regulatory systems (TCSs) to sense and adapt to changing environments. Among them, the Roc (regulation of cup) system is a one-of-a-kind network of branched TCSs, composed of two histidine kinases (HKs-RocS1 and RocS2) interacting with three response regulators (RRs-RocA1, RocR, and RocA2), which regulate virulence, antibiotic resistance, and biofilm formation. Based on extensive work on the Roc system, previous data suggested the existence of other key regulators yet to be discovered. In this work, we identified PA4080, renamed RocA3, as a fourth RR that is activated by RocS1 and RocS2 and that positively controls the expression of the cupB operon. Comparative genomic analysis of the locus identified a gene-rocR3-adjacent to rocA3 in a subpopulation of strains that encodes a protein with structural and functional similarity to the c-di-GMP phosphodiesterase RocR. Furthermore, we identified a fourth branch of the Roc system consisting of the PA2583 HK, renamed RocS4, and the Hpt protein HptA. Using a bacterial two-hybrid system, we showed that RocS4 interacts with HptA, which in turn interacts with RocA1, RocA2, and RocR3. Finally, we mapped the pangenomic RRs repertoire, establishing a comprehensive view of the plasticity of such regulators among clades of the species. Overall, our work provides a comprehensive inter-species definition of the Roc system, nearly doubling the number of proteins known to be involved in this interconnected network of TCSs controlling pathogenicity in Pseudomonas species.
Predicting input signals of transcription factors in Escherichia coli
Trouillon, Julian; Huber, Alexandra E.; Trabesinger, Yannik; et al. (2025)
Molecular Systems Biology
The activity of bacterial transcription factors (TFs) is typically modulated through direct interactions with small molecules. However, these input signals remain unknown for most TFs, even in well-studied model bacteria. Identifying these signals typically requires tedious experiments for each TF. Here, we develop a systematic workflow for the identification of TF input signals in bacteria based on metabolomics and transcriptomics data. We inferred the activity of 173 TFs from published transcriptomics data and determined the abundance of 279 metabolites across 40 matched experimental conditions in Escherichia coli. By correlating TF activities with metabolite abundances, we successfully identified previously known TF-metabolite interactions and predicted novel TF effector metabolites for 41 TFs. To validate our predictions, we conducted in vitro assays and confirmed a predicted effector metabolite for LeuO. As a result, we established a network of 80 regulatory interactions between 71 metabolites and 41 E. coli TFs. This network includes 76 novel interactions that encompass a diverse range of chemical classes and regulatory patterns, bringing us closer to a comprehensive TF regulatory network in E. coli.
Determination of the two-component systems regulatory network reveals core and accessory regulations across Pseudomonas aeruginosa lineages
Trouillon, Julian; Imbert, Lionel; Villard, Anne-Marie; et al. (2021)
Nucleic Acids Research
Pseudomonas aeruginosa possesses one of the most complex bacterial regulatory networks, which largely contributes to its success as a pathogen. However, most of its transcription factors (TFs) are still uncharacterized and the potential intra-species variability in regulatory networks has been mostly ignored so far. Here, we used DAP-seq to map the genome-wide binding sites of all 55 DNA-binding two-component systems (TCSs) response regulators (RRs) across the three major P. aeruginosa lineages. The resulting networks encompass about 40% of all genes in each strain and contain numerous new regulatory interactions across most major physiological processes. Strikingly, about half of the detected targets are specific to only one or two strains, revealing a previously unknown large functional diversity of TFs within a single species. Three main mechanisms were found to drive this diversity, including differences in accessory genome content, as exemplified by the strain-specific plasmid in IHMA87 outlier strain which harbors numerous binding sites of conserved chromosomally-encoded RRs. Additionally, most RRs display potential auto-regulation or RR-RR cross-regulation, bringing to light the vast complexity of this network. Overall, we provide the first complete delineation of the TCSs regulatory network in P. aeruginosa that will represent an important resource for future studies on this pathogen.

Publications 1 - 8 of 8

Julian Trouillon

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