Biology subjects

Fondi, M.

Publications and source records attributed to Fondi, M..

At least 19 recordsLinked to original sources

bioRxiv2026

Development of a stable microbial community for the study of plasmid-mediated antimicrobial resistance in a continuous culturing device

Horizontal gene transfer (HGT) is a major contributor to the spread of antimicrobial resistance (AMR) in microbial communities, particularly through conjugative plasmids. The dynamics of the spread of these plasmids in a susceptible microbial community requires a defined and controllable in vitro system, which is currently lacking from existing laboratory evolution systems. Here we describe the development of TriComm, an engineered microbial community of three strains with complementary amino acid auxotrophies, maintained in continuous culture under real-time optical and fluorescence monitoring. We show that two conjugative plasmids carrying resistance genes (blaOXA-48 and mcr-1) generally rescued TriComm from collapse under antimicrobial treatment, and that this protection was dependent on conjugative transfer. Community composition remained stable across most conditions, including after the AMR plasmid had spread through the population. Through mathematical modeling we predict that modulating both drug efficacy and conjugation rate can lead to the collapse of the community, suggesting potential strategies to limit the spread of AMR via HGT.

microbiology↗

bioRxiv2026

From code to natural language: MErlin - a multiomics toolkit for bacterial epigenomics delivered as Claude agent skill.

Interpreting a bacterial methylome is a multi-omics problem. It requires integrating modified-base calls with genome annotation, motif inventories, methyltransferase genotypes, transcript abundance, replichore position and, increasingly, chromosome conformation. These data types are commonly generated in incompatible formats, use inconsistent sequence and gene identifiers, and originate from different analytical workflows. The relevant algorithms are available, but assembling them into a coherent and statistically defensible analysis remains a substantial data-integration and interface problem. We present MErlin (Methylation-driven Expression & Regulation Linkage in Interacting Nuclear-domains), a multi-omics toolkit comprising seventeen composable modules, from basecalled modBAM files to ranked gene-level evidence and a self-contained HTML report. MErlin is distributed both as a conventional Python package and as an agent skill: a structured, version-controlled layer of procedural knowledge that enables a compatible large language model (LLM) assistant to select and operate the audited package without generating a new analysis implementation for each request. This design treats natural language as an interface to fixed analytical operations rather than as a substitute for tested scientific software. The skill encodes module-selection rules, mandatory preflight checks, questions that require human input, design-to-inference constraints, and interpretation guidance. We describe MErlin's architecture and statistics, validate it against a synthetic dataset with planted ground truth, and illustrate the conversational interface on a real methylome-transcriptome comparison in Pseudoalteromonas haloplanktis TAC125. MErlin is open source and available at https://github.com/IacopoPasseri/MErlin

bioinformatics↗

bioRxiv2025

From microbiome to sperm motility traits: An inside out perspective

Growing interest in the relationship between microbiome composition and host biology has revealed the many ways host-associated microbes influence physiology, ecology, and evolution. However, microbial communities associated with reproductive organs - and their roles in reproduction - remain poorly understood. Here, we characterized the skin- and ejaculate-associated microbiomes in an internally fertilizing fish and tested whether microbial diversity and specific bacterial taxa correlate with sperm motility traits key for reproductive success. We used the guppy (Poecilia reticulata), a well-established model in ecology and evolutionary biology with well-characterised reproductive physiology. In guppies, sperm velocity is a validated predictor of male reproductive performance, making them a powerful system for exploring microbiome-fertility interactions. Our analyses reveal a correlation between skin microbiome diversity and sperm performance. Notably, increased skin microbiome total richness is associated with reduced sperm velocity, whereas no significant associations were detected for ejaculate-associated microbiomes. We also identified bacterial taxa across both tissues that were positively or negatively linked with sperm performance. These findings suggest that, while the ejaculate-associated microbiome may directly influence sperm traits, the skin microbiome could serve as a proxy for reproductive potential by reflecting systemic physiological and immunological states associated with fertility.

microbiology↗

bioRxiv2024

Engineering the Marine Pseudoalteromonas haloplanktis TAC125 via pMEGA Plasmid Targeted Curing Using PTasRNA Technology

Marine bacteria that have adapted to thrive in extreme environments, such as Pseudoalteromonas haloplanktis TAC125 (PhTAC125), offer a unique biotechnological potential. The discovery of an endogenous megaplasmid (pMEGA) raised questions about its metabolic impact and functional role in this strain. This study aimed at streamlining the host genetic background by curing PhTAC125 from the pMEGA plasmid using a sequential genetic approach. We combined homologous recombination by exploiting a suicide vector with the PTasRNA gene silencing technology to interfere with pMEGA replication machinery. This approach led to the construction of the novel PhTAC125 KrPL2 strain, cured from the pMEGA plasmid, which exhibited no significant differences in the growth behaviour, though showcasing enhanced resistance to oxidative stress and a reduced capability of biofilm formation. These findings represent a significant achievement for understanding of the role of pMEGA plasmid and for the biotechnological applications of PhTAC125 in recombinant protein production. This opens up the possibility to exploit pMEGA valuable genetic elements and further advancing the genetic tools for PhTAC125.

microbiology↗

bioRxiv2024

Insights into optimization of oleaginous fungi - genome-scale metabolic reconstruction and analysis of Umbelopsis sp. WA50703

Oleaginous fungi, known for their high lipid content--up to 80% of their dry mass--are of significant interest for biotechnological applications, particularly in biofuel and fatty acid production. Among these, the genus Umbelopsis, a common soil saprotroph of the Mucoromycota phylum, stands out for its rapid growth, low nutritional requirements, and ability to produce substantial amounts of lipids, especially polyunsaturated fatty acids (PUFAs). Despite previous studies on lipid production in Umbelopsis, metabolic engineering has been underexplored. This study fills that gap by presenting the first comprehensive metabolic model for Umbelopsis sp. WA50703, encompassing 2413 metabolites, 2216 reactions, and 1629 genes (iMD1629). The model demonstrated strong predictive accuracy, correctly predicting metabolic capabilities in 82.1% of cases when evaluated against experimental data. Using the Flux Scanning based on Enforced Objective Flux (FSEOF) algorithm, the study identified 33 genes linked to 23 metabolic reactions. Notably, reactions catalysed by acetyl-CoA carboxylase and carbonic anhydrase emerged as prime candidates for up-regulation. These findings provide a solid framework for future metabolic engineering efforts to optimize PUFA production in Umbelopsis strains. ImportanceUmbelopsis strains are capable of producing valuable compounds like polyunsaturated fatty acids (PUFAs). These compounds are essential for human health, found in various foods and supplements that support heart and brain function. In this study we developed a computer model to better understand how this fungus works at a metabolic level, guiding further research investigations towards optimization of PUFAs production in a cost-effective way. This research lays the groundwork for future innovations in metabolic engineering of Umbelopsis PUFA production leading to healthier food options and a more sustainable food system, directly impacting everyday life.

systems biology↗

bioRxiv2024

The acquisition of additional control over quorum sensing regulation buffers noise in microbial growth dynamics

Quorum sensing (QS) is a cell-to-cell communication system used by bacteria to act collectively. Often, bacteria possess more than one QS regulatory module that form complex regulatory networks. Presumably, these configurations have evolved through the integration of novel transcription factors into the native regulatory systems. The selective advantages provided by these alternative configurations on QS-related phenotypes is poorly predictable only based on their underlying network structure. Here we show that the acquisition of extra regulatory modules of QS has important consequences on the overall regulation of microbial growth dynamics by significantly reducing the variability in the final size of the population in Burkholderia. We mapped the distribution of horizontally transferred QS modules in extant bacterial genomes, finding that these tend to add up to already-present modules in the majority of cases, 63.32%. We then selected a strain harboring two intertwined QS modules and,using mathematical modelling, we predicted an intrinsic ability of the newly acquired module to buffer noise in growth dynamics. We experimentally validated this prediction choosing one strain possessing both systems, deleting one of the two and measuring key growth parameters and QS synthase expression. We extended such considerations on two other strains naturally implementing the two versions of the QS regulation studied herein. Finally, using transcriptomics, we show that the de-regulation of metabolism likely plays a key role in differentiating the two configurations. Our results shed light on the role of additional control over QS regulation and illuminate on the possible phenotypes that may arise after HGT events.

systems biology↗

bioRxiv2023

The pan-epigenome of the symbiotic nitrogen fixing bacterium Sinorhizobium meliloti unravels unexpected variability of DNA-methylation profiles in closely related strains

In prokaryotes, DNA methylation has been found to be involved in several mechanisms, such as DNA repair, DNA-protein interactions, gene expression, cell cycle progression and self-DNA recognition (the Restriction-Modification systems). Studies on representatives from the same bacterial species have found that genome-wide DNA methylation patterns can be highly variable and may affect phenotypic variation and gene transfer among closely related strains. However, broader evolutionary studies on such epigenomic variation in bacteria are still scarce. Here, we addressed this point by performing an epigenomic analysis on 21 strains of the facultative plant symbiotic nitrogen-fixing alphaproteobacterium Sinorhizobium meliloti. Strains of these species are characterized by a divided (multipartite) genome structure, including a chromosome, a chromid and a (more recently acquired) megaplasmid. Since these strains display extensive genomic and phenotypic variation, they are good models to test evolutionary hypotheses on the relationships among epigenomic signatures, genome structure evolution and phenotypic switches. Results showed the presence of a wide pan-epigenome with 16 DNA methylated motifs, including both 4mC and 6mA palindromic and nonpalindromic motifs. While 9 motifs have been found methylated by all strains, the remaining had differential methylation between S. meliloti strains, constituting a dispensable epigenome. Differences in frequency of methylation were found among replicons, with the megaplasmid and the additional plasmids displaying several motifs with different methylation frequency with respect to the chromosome and the chromid. Moreover, differences between coding, upstream and intergenic regions, were found, suggesting that DNA methylation at specific motifs may play a role in gene regulation and consequently in phenotypic variability among strains. Altogether, our data indicate the presence of a large epigenomic diversity in S. meliloti, with epigenome signatures differing between replicons, reflecting their timing of evolutionary acquisition in S. meliloti genomes and suggesting a role of DNA methylation in the variability of gene expression among strains.

genomics↗

bioRxiv2022

Metabolic robustness to growth temperature of cold adapted bacterium

Microbial communities experience continuous environmental changes, among which temperature fluctuations are arguably the most impacting. This is particularly important considering the ongoing global warming but also in the "simpler" context of seasonal variability of sea-surface temperature. Understanding how microorganisms react at the cellular level can improve our understanding of possible adaptations of microbial communities to a changing environment. In this work, we investigated which are the mechanisms through which metabolic homeostasis is maintained in a cold-adapted bacterium during growth at temperatures that differ widely (15 and 0{degrees}C). We have quantified its intracellular and extracellular central metabolomes together with changes occurring at the transcriptomic level in the same growth conditions. This information was then used to contextualize a genome-scale metabolic reconstruction and to provide a systemic understanding of cellular adaptation to growth at two different temperatures. Our findings indicate a strong metabolic robustness at the level of the main central metabolites, counteracted by a relatively deep transcriptomic reprogramming that includes changes in gene expression of hundreds of metabolic genes. We interpret this as a transcriptomic buffering of cellular metabolism, able to produce overlapping metabolic phenotypes despite the wide temperature gap. Moreover, we show that metabolic adaptation seems to be mostly played at the level of few key intermediates (e.g. phosphoenolpyruvate) and in the cross-talk between the main central metabolic pathways. Overall, our findings reveal a complex interplay at gene expression level that contributes to the robustness/resilience of core metabolism, also promoting the leveraging of state-of-the-art multi-disciplinary approaches to fully comprehend molecular adaptations to environmental fluctuations.

systems biology↗

bioRxiv2022

The selective force driving metabolic operon assembly

The evolution of operons has puzzled evolutionary biologists since their discovery and many theories exist to explain their emergence and spreading. The presence of several plausible hypotheses dealing with operon emergence/evolution/spreading is indicative of the absence of a universal causal factor for this evolutionary process. Here, we argue that the way in which DNA replication and cell division are coupled in microbial species introduces an additional selective force that may be responsible for the clustering of functionally related genes on chromosomes. We interpret this as a preliminary and necessary step in operon formation. Specifically, we start from the observation that during DNA replication differences in copy number of genes that are found at distant loci on the same chromosome arm exist. We provide theoretical considerations suggesting that, when genes of the same metabolic process are far away on the chromosome, this results in perturbations to metabolic homeostasis. By formalizing the effect of DNA replication on metabolic homeostasis based on Metabolic Control Analysis, we show that the above situation provides a selective force that can drive the formation of gene clusters and operons. Finally, we confirmed that, in present-day genomes, this force is significantly stronger in those species where the average number of active replication forks is larger and quantify the theoretical contribution of this feature on the distribution of extant gene clusters and operons.

systems biology↗

bioRxiv2022

Modelling the metabolic consequences of antimicrobial exposure

Besides genetic mutations, the metabolic state of bacterial cells represents another driving factor in the emergence of antimicrobial resistance and in the actual efficacy of treatments. In this direction, studying how bacteria reprogram their metabolism when facing antimicrobial exposure is crucial to enhance our ability to limit the development and spread of antibiotic resistance. Here we have studied the metabolic consequences of antimicrobial exposure in bacteria using an integrated approach that exploits transcriptomics and computational modelling. Specifically, we asked whether common metabolic strategies emerge during the exposure to antimicrobials, regardless of the kind of antimicrobial used or, on the contrary, antimicrobial-specific pathways exist. To this purpose, we have used an heterogeneous dataset from six published studies on Escherichia coli exposed to different concentrations/types of compounds. We show that experimental condition, not antimicrobial exposure, is the factor that influences the most the resulting metabolic networks. However, despite condition-dependent metabolic signatures being evident, specific changes in flux distributions by antimicrobial exposed cells could be identified. In particular, purine and pyrimidine biosynthesis, and cofactor and prosthetic group biosynthesis were commonly affected by all considered antimicrobials. This suggests the presence of general metabolic strategies to face the stress posed by antimicrobial exposure and that, in turn, may represent an untapped resource for the fight against microbial infections. Finally, our analysis predicted an overall metabolic rewiring following bacteriostatic vs. bactericidal drug exposure that is in line with the current knowledge about the effects of these two classes of compounds on microbial metabolic phenotypes. IMPORTANCEA mechanistic understanding of microbial metabolic reprogramming during antimicrobial exposure is key to facilitate the discovery of new resistance mechanisms and to identify novel areas of intervention to face microbial infections. This study shows how the integration of transcriptomic data and genome-scale metabolic modelling can be used to address this critical issue, and to trace general metabolic strategies exploited by bacteria to face the stress posed by antimicrobial drugs.

systems biology↗

bioRxiv2022

Extraction and analysis of methylation features from Pacific Biosciences SMRT reads using MeStudio

MotivationDNA methylation is the most relevant epigenetic information, present in eukaryotes and prokaryotes, and is related to several biological phenomena, from cellular differentiation to control of gene flow, pathogenesis and virulence. The widespread use of third-generation sequencing technologies allows direct and easy detection of genome-wide methylation profiles, offering increasing opportunities to understand and exploit the epigenomics landscape. ResultsWe introduce MeStudio, a pipeline which allows to analyse and combine genome-wide methylation profiles with genomic features. Outputs report the presence of DNA methylation in coding sequences, noncoding sequences, intergenic sequences, and sequences upstream to CDS. We show the usage and performances of MeStudio on a set of single-molecule real time sequencing outputs from the bacterial species Sinorhizobium meliloti. Availability and ImplementationMeStudio is written in Python, Bash and C and is freely available under an open source GPLv3 license at https://github.com/combogenomics/MeStudio Supplementary informationSupplementary data are available at Bioinformatics online. Contactcombo.unifi@gmail.com

bioinformatics↗

bioRxiv2021

Modelling hCDKL5 heterologous expression in bacteria

hCDKL5 refers to the human cyclin-dependent kinase that is primarily expressed in the brain where it exerts its function in several neuron districts. Mutations in its coding sequence are often causative of hCDKL5 deficiency disorder. The large-scale recombinant production of hCDKL5 is desirable to boost the translation of current therapeutic approaches into the clinic. However, this is hampered by the following features: i) almost two-thirds of hCDKL5 sequence are predicted to be intrinsically disordered, making this region more susceptible to proteolytic attack; ii) the cytoplasmic accumulation of the enzyme in eukaryotic host cells is associated to toxicity. The bacterium Pseudoalteromonas haloplanktis TAC125 (PhTAC125) is the only prokaryotic host in which the full-length production of hCDKL5 has been demonstrated. To date, a system-level understanding of the metabolic burden imposed by hCDKL5 production is missing, although it would be crucial for the upscaling of the production process. Here, we have combined experimental data on protein production and nutrients assimilation with metabolic modelling to infer the global consequences of hCDKL5 production in PhTAC125 and to identify potential overproduction targets. Our analyses showed a remarkable accuracy of the model in simulating the recombinant strain phenotype and also identified priority targets for optimized protein production.

systems biology↗

bioRxiv2021

The acquisition of additional feedback loops may optimize and speed up the response of quorum sensing

1.Bacterial quorum sensing (QS) is a cell-to-cell communication system in which specific signals are activated to coordinate, for example, pathogenic behaviors and help bacteria collectively respond to perturbations. QS in Gram-negative bacteria is typically regulated by a N-acyl-homoserine lactone (AHL) molecules-mediated system, homologous of Vibrio fischeri LuxI-R. In many cases, bacteria possess more than one QS system, based on different types of molecules, that interact through a complex regulatory network. Presumably, these configurations have emerged over time from simpler ones through the acquisition of novel players (e.g. transcription factors) that have been successfully integrated into the native regulatory systems. However, the advantages provided by these alternative/additional configurations on QS-related phenotypes is poorly predictable only based on their underlying network structure. Here, we have adopted a modelling approach to infer the possible improvements conferred by the acquisition of additional control over bacterial regulation of QS. We use the Burkholderia genus as a case study because some of these strains, besides the LuxIR-like system (named CepIR), possess an integrated regulatory module named CciIR that interferes with the CepIR system through the implementation of several positive and negative control loops. Being associated to a genomic island (cci island), this additional module is prone to being horizontally transferred, giving rise to a potentially patchy genomic distribution and, in turn, to a complete (CepIR and CciIR systems together) vs. core (CepIR only) organization of QS regulation in this group of microorganisms. By using both deterministic and stochastic modelling we show that, upon their activation, the two regulatory schemes may lead to different phenotypes and to distinct responses to the extracellular concentration of signalling molecules. In particular, our simulations show that the presence of the additional regulatory module may confer specific improvements, including a faster response time and optimized control of QS regulation. Interestingly, some of these features may be particularly advantageous during host invasion, thus highlighting once more the importance of QS in the establishment and maintenance of bacterial infections.

systems biology↗

bioRxiv2021

Scaling down the microbial loop: data-driven modelling of growth interactions in a diatom-bacterium co-culture

An intricate set of interactions characterizes marine ecosystems. One of the most important is represented by the so-called microbial loop, which includes the exchange of dissolved organic matter (DOM) from phototrophic organisms to heterotrophic bacteria. Here, it can be used as the major carbon and energy source. Arguably, this interaction is one of the foundations of the entire ocean food-web. Carbon fixed by phytoplankton can be redirected to bacterial cells in two main ways; either i) bacteria feed on dead (eventually lysed) phytoplankton cells or ii) DOM is actively released by phytoplankton cells (a widespread process that may result in up to 50% of the fixed carbon leaving the cell). In this work, we have set up a co-culture of the model diatom Phaeodactylum tricornutum and the model chemoheterotrophic bacterium Pseudoalteromonas haloplanktis TAC125 and used this system to study the interactions between these two representatives of the microbial loop. We show that the bacterium can indeed thrive on diatom-derived carbon and that this growth can be sustained by both diatom dead cells and diatom-released compounds. These observations were formalized in a network of putative interactions between P. tricornutum and P. haloplanktis and implemented in a mathematical model that reproduces the observed co-culture dynamics, suggesting that our hypotheses on the interactions occurring in this two-player system can accurately explain the experimental data.

systems biology↗

bioRxiv2019

A Virtual Nodule Environment (ViNE) for modelling the inter-kingdom metabolic integration during symbiotic nitrogen fixation

Biological associations are often premised upon metabolic cross-talk between the organisms, with the N2-fixing endosymbiotic relationship between rhizobia and leguminous plants being a prime example. Here, we report the in silico reconstruction of a metabolic network of a Medicago truncatula plant nodulated by the bacterium Sinorhizobium meliloti. The nodule tissue of the model contains five spatially distinct developmental zones and encompasses the metabolism of both the plant and the bacterium. Flux balance analysis (FBA) suggested that the majority of the metabolic costs associated with symbiotic nitrogen fixation are directly related to supporting nitrogenase activity, while a minority is related to the formation and maintenance of nodule and bacteroid tissue. Interestingly, FBA simulations suggested there was a non-linear relationship between the rate of N2-fixation per gram of nodule and the rate of plant growth; increasing the N2-fixation efficiency was associated with diminishing returns in terms of plant growth. Evaluating the metabolic exchange between the symbiotic partners provided support for: i) differentiating bacteroids having access to sugars (e.g., sucrose) as a major carbon source, ii) ammonium being the major nitrogen export product of N2-fixing bacteria, and iii) N2-fixation being dependent on the transfer of protons from the plant cytoplasm to the bacteria through acidification of the peribacteroid space. Our simulations further suggested that the use of C4-dicarboxylates by N2-fixing bacteroids may be, in part, a consequence of the low concentration of free oxygen in the nodule limiting the activity of the plant mitochondria. These results demonstrate the power of this integrated model to advance our understanding of the functioning of legume nodules, and its potential for hypothesis generation to guide experimental studies and engineering of symbiotic nitrogen fixation.

systems biology↗

bioRxiv2019

Diauxie and co-utilization are not exclusive during growth in nutritionally complex environments

The classic view of microbial growth strategy when multiple carbon sources are available states that they either metabolize them sequentially (diauxic growth) or simultaneously (co-utilization). This perspective is biased by the fact that this process has been mainly analysed in over-simplified laboratory settings, i.e. using a few model microorganisms and growth media containing only two alternative compounds. Models concerning the mechanisms and the dynamics regulating nutrients assimilation strategies in conditions that are closer to the ones found in natural settings (i.e. with many alternative carbon/energy sources) are missing. Here, we show that bacterial co-utilization and sequential uptake of multiple substrates can coexist when multiple possible nutrients are provided in the same growth experiment, leading to an efficient exploitation of nutritionally complex settings. The order of nutrient uptake is determined by the actual biomass yield (and growth rate) that can be achieved when the same compounds are provided as single carbon sources. Finally, using two alternative theoretical models we show that this complex metabolic phenotype can be explained by a tight regulation process that allows microbes to actively modulate the different assimilatory pathways involved.

systems biology↗

bioRxiv2019

A high-resolution, chromosome-assigned Komodo dragon genome reveals adaptations in the cardiovascular, muscular, and chemosensory systems of monitor lizards

Monitor lizards are unique among ectothermic reptiles in that they have a high aerobic capacity and distinctive cardiovascular physiology which resembles that of endothermic mammals. We have sequenced the genome of the Komodo dragon (Varanus komodoensis), the largest extant monitor lizard, and present a high resolution de novo chromosome-assigned genome assembly for V. komodoensis, generated with a hybrid approach of long-range sequencing and single molecule physical mapping. Comparing the genome of V. komodoensis with those of related species showed evidence of positive selection in pathways related to muscle energy metabolism, cardiovascular homeostasis, and thrombosis. We also found species-specific expansions of a chemoreceptor gene family related to pheromone and kairomone sensing in V. komodoensis and several other lizard lineages. Together, these evolutionary signatures of adaptation reveal genetic underpinnings of the unique Komodo sensory, cardiovascular, and muscular systems, and suggest that selective pressure altered thrombosis genes to help Komodo dragons evade the anticoagulant effects of their own saliva. As the only sequenced monitor lizard genome, the Komodo dragon genome is an important resource for understanding the biology of this lineage and of reptiles worldwide.

genomics↗

bioRxiv2018

An synthetic microbial loop for modelling heterotroph-phototroph metabolic interactions

Marine ecosystems are characterized by an intricate set of interactions among their representatives. One of the most important occurs through the exchange of dissolved organic matter (DOM) provided by phototrophs and used by heterotrophic bacteria as their main carbon and energy source. This metabolic interaction represents the foundation of the entire ocean food-web.\n\nHere we have assembled a synthetic ecosystem to assist the systems-level investigation of this biological association. This was achieved building an integrated, genome-scale metabolic reconstruction using two model organisms (a diatom Phaeodactylum tricornutum and an heterotrophic bacterium, Pseudoalteromonas haloplanktis) to explore and predict their metabolic interdependencies. The model was initially analysed using a constraint-based approach (Flux Balance Analysis, FBA) and then turned into a dynamic (dFBA) model to simulate a diatom-bacteria co-culture and to study the effect of changes in growth parameters on such a system. Finally, we developed a simpler dynamic ODEs system that, fed with dFBA results, was able to qualitatively describe this synthetic ecosystem and allowed performing stochastic simulations to assess the effect of noise on the overall balance of this co-culture.\n\nWe show that our model recapitulates known metabolic cross-talks of a phototroph-heterotroph system, including mutualism and competition for inorganic ions (i.e. phosphate and sulphate). Further, the dynamic simulation predicts realistic growth rate for both the diatom and the bacterium and a steady state balance between diatom and bacterial cell concentration that matches those determined in experimental co-cultures. This steady state, however, is reached following an oscillatory trend, a behaviour that is typically observed in the presence of metabolic co-dependencies. Finally, we show that, at high diatom/bacteria cell concentration ratio, stochastic fluctuations can lead to the extinction of bacteria from the co-culture, causing the explosion of diatom population. We anticipate that the developed synthetic ecosystem will serve in the future as a basis for the generation of testable hypotheses and as a scaffold for integrating and interpreting-omics data from experimental co-cultures.

systems biology↗