Biology subjects

Pereto, J.

Publications and source records attributed to Pereto, J..

8 recordsLinked to original sources

bioRxiv2026

A metabolic model based on a pangenome core unveils new biochemical features of the phytopathogen Xylella fastidiosa

Xylella fastidiosa is a xylem-limited phytopathogenic bacterium responsible for severe diseases in many economically important crops. Despite its impact, its metabolism remains poorly characterized due to fastidious growth and the limited availability of defined culture media. Here, we reconstruct the first pangenome-based genome-scale metabolic model for X. fastidiosa, integrating conserved metabolic functions from 18 strains across five subspecies. The resulting core model, iXfcore, is manually curated and used to explore the species metabolic capabilities. Model simulations predict minimal nutritional requirements that guided us in the formulation of defined media supporting biofilm formation in vitro, providing validation of the models predictive capacity. Network analysis also identifies a previously undescribed pathway enabling growth on acetate as a sole carbon source. In addition, the model predicts the overproduction of polyamines, compounds linked to virulence in other phytopathogens. Experimental analyses confirm the production and secretion of polyamines in multiple X. fastidiosa strains, providing the first evidence of this capability. These results suggest that polyamine biosynthesis may represent an uncharacterized virulence factor for X. fastidiosa, potentially contributing to protection against host-induced oxidative stress. Overall, iXfcore provides a systems-level framework to investigate X. fastidiosa metabolism, generate testable hypotheses on its physiology and virulence, and support future strain-specific models and studies of host-pathogen metabolic interactions.

systems biology↗

bioRxiv2025

Flux modelling analysis reveals the metabolic impact of cryptic plasmids and environmental conditions in probiotic Escherichia coli Nissle 1917

Escherichia coli Nissle 1917 (EcN) is a well-characterized Gram-negative probiotic distinguished by its unique, strain-specific physiology. Genome-scale metabolic models (GEMs) are powerful tools for elucidating metabolic traits and predicting genotype-phenotype relationships. Although several EcN GEMs have been published, none have explicitly represented its probiotic physiology. Here, we present a manually curated GEM of EcN that, for the first time, incorporates the energetic costs associated with its cryptic plasmids. Inclusion of a plasmid-specific module improved biomass yield predictions and overall model accuracy, providing a more physiologically realistic representation of EcN metabolism. Using COBRA methodologies and possibilistic metabolic flux analysis, this model and previous EcN reconstructions were systematically compared to evaluate the trade-off between model complexity and predictive performance. The analysis revealed that increased structural detail does not necessarily enhance quantitative accuracy and that predictive reliability depends on both computational methodology and model context. Metabolomic profiling under gut-like anaerobic conditions further showed that EcN exhibits a distinctive metabolic phenotype, characterized by elevated amino acid consumption and enhanced short-chain fatty acid production. These findings highlight the unique probiotic physiology of EcN and demonstrate the utility of metabolic modeling for reproducing and exploring such traits. Overall, this study provides a quantitatively reliable and physiologically relevant framework for modeling E. coli Nissle 1917 and related commensal bacteria, supporting advances in probiotic engineering, synthetic biology, and bioprocess design. Graphical Abstract SummaryThis study presents a manually curated genome-scale model of Escherichia coli Nissle 1917 that accounts for the metabolic cost of its cryptic plasmids. Through systematic comparison with previous reconstructions and validation against fluxomics datasets, the models improved accuracy in predicting growth and fluxes. Simulations and experiments under gut-like conditions provide new insights into EcNs unique probiotic traits. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=120 SRC="FIGDIR/small/688048v2_ufig1.gif" ALT="Figure 1"> View larger version (49K): org.highwire.dtl.DTLVardef@6c8c98org.highwire.dtl.DTLVardef@8263e3org.highwire.dtl.DTLVardef@6c04c3org.highwire.dtl.DTLVardef@1acb811_HPS_FORMAT_FIGEXP M_FIG C_FIG

systems biology↗

bioRxiv2023

Maltodextrin administration ameliorates brain pathology in a mouse model of mitochondrial disease

Mitochondrial dysfunction lead to a wide group of progressive and fatal pathologies known as mitochondrial diseases (MD). One of the most common pediatric representation of MD is Leigh Syndrome, affecting 1/40.000 births. LS is characterized by neurodegeneration in specific brain areas, such as brainstem and basal ganglia, and by respiratory and motor alterations. However, the results obtained from clinical trials based on antioxidant therapies are controversial. Thus, the development novel antioxidant strategy is required to improve the efficacy of current palliative treatments. In this regard, Ndufs4KO mouse model is a suitable model to test new drugs in the field of MD and LS. Therefore, we set to assess the therapeutic potential of oral administration of Micrococcus luteus, a high-antioxidant content microorganism. Incidentally, we identified that while M. luteus administration did not possess any beneficial actions, the cryopreservant maltodextrin (MDX), included in the preparation, ameliorated the phenotype of Ndufs4KO mice. Our results show that MDX treatment at a concentration of 30 g/L increased lifespan and reduced microglial reaction compared to vehicle-treated Ndufs4KO mice. However, no improvement in locomotion nor respiratory function was observed in MDX-treated mice compared to vehicle-treated Ndufs4KO mice. Metataxonomic characterization of intestinal microbiome identified differential profiles in Ndufs4KO mice at the genus level. Furthermore, MDX treatment increased the variability of the abundance of Akkermansia sp. Thus, this work paves the way for further studies to confirm the therapeutic potential of MDX in mitochondrial disease.

neuroscience↗

bioRxiv2023

A 3D printed plastic frame deeply impacts yeast cell growth

Solid State Fermentation (SSF) processes have been explored for yeast growth and protein and metabolites production. However, most of these processes lack standardization. In this work, we present a polylactic acid (PLA) 3D printed matrix that dramatically enhances yeast growth when embedded in liquid media compared to equivalent static cultures, and changes yeast expression patterns at the proteome level. Moreover, differences in sugar assimilation and ethanol production, as the main product of alcoholic fermentation, are observed. Our results suggest that these matrixes may be useful for a vast range of biotechnological applications based on yeast fermentation.

microbiology↗

bioRxiv2018

Microbial communities of the Mediterranean rocky coast: ecology and biotechnological potential

Microbial communities from harsh environments hold great promise as sources of biotechnologically-relevant strains. In the present work, we have deeply characterized the microorganisms from three different rocky locations of the Mediterranean coast, an environment characterised by being subjected to harsh conditions such as high levels of irradiation and large temperature and salinity fluctuations. Through culture-dependent and culture-independent techniques, we have retrieved a complete view of the ecology and functional aspects of these communities and assessed the biotechnological potential of the cultivable microorganisms. A culture-independent approach through high-throughput 16S rRNA amplicon sequencing revealed that all three locations display very similar microbial communities, suggesting that there is a stable community associated to the sampled region, with Stanieria cyanosphaera, Rubrobacter sp. and the families Flammeovirgaceae, Phyllobacteriaceae, Rhodobacteraceae and Trueperaceae being the most abundant taxa. Furthermore, shotgun metagenomic sequencing results were in concordance with the high-thoughput 16S rRNA, and allowed a description of the eukaryotic and archaeal members of the community, which were abundant in Ascomycota and halotolerant archaea, respectively. The culture-dependent approach yielded a collection of 100 isolates (mainly pigmented), out of which 12 displayed high antioxidant activities, as proved with two in vitro (hydrogen peroxide and DPPH) and an in vivo (model organism C. elegans) assays.

microbiology↗

bioRxiv2018

Bioprospecting the solar panel microbiome: high-throughput screening for antioxidant bacteria in a Caenorhabditis elegans model

Microbial communities that are exposed to sunlight typically share a series of adaptations to deal with the radiation they are exposed to, including efficient DNA repair systems, pigment production and protection against oxidative stress, which makes these environments good candidates for the search of novel antioxidant microorganisms. In this research project, we isolated potential antioxidant pigmented bacteria from a dry and highly-irradiated extreme environment: solar panels. High-throughput in vivo assays using Caenorhabiditis elegans as an experimental model demonstrated the high antioxidant and ultraviolet-protection properties of these bacterial isolates that proved to be rich in carotenoids. Our results suggest that solar panels harbor a microbial community that includes strains with potential applications as antioxidants.

microbiology↗

bioRxiv2018

Influence of pathway topology and functional class on the molecular evolution of human metabolic genes

Metabolic networks comprise thousands of enzymatic reactions functioning in a controlled manner and have been shaped by natural selection. Thanks to the genome data, the footprints of adaptive (positive) selection are detectable, and the strength of purifying selection can be measured. This has made possible to know where, in the metabolic network, adaptive selection has acted and where purifying selection is more or less strong and efficient. We have carried out a comprehensive molecular evolutionary study of all the genes involved in the human metabolism. We investigated the type and strength of the selective pressures that acted on the enzyme-coding genes belonging to metabolic pathways during the divergence of primates and rodents. Then, we related those selective pressures to the functional and topological characteristics of the pathways. We have used DNA sequences of all enzymes (956) of the metabolic pathways comprised in the HumanCyc database, using genome data for humans and five other mammalian species.\n\nWe have found that the evolution of metabolic genes is primarily constrained by the layer of the metabolism in which the genes participate: while genes encoding enzymes of the inner core of metabolism are much conserved, those encoding enzymes participating in the outer layer, mediating the interaction with the environment, are evolutionarily less constrained and more plastic, having experienced faster functional evolution. Genes that have been targeted by adaptive selection are endowed by higher out-degree centralities than non-adaptive genes, while genes with high in-degree centralities are under stronger purifying selection. When the position along the pathway is considered, a funnel-like distribution of the strength of the purifying selection is found. Genes at bottom positions are highly preserved by purifying selection, whereas genes at top positions, catalyzing the first steps, are open to evolutionary changes.\n\nThese results show how functional and topological characteristics of metabolic pathways contribute to shape the patterns of evolutionary pressures driven by natural selection and how pathway network structure matters in the evolutionary process that shapes the evolution of the system.

systems biology↗

bioRxiv2017

A genome-scale study of metabolic complementation in endosymbiotic consortia: the case of the cedar aphid

Bacterial endosymbionts and their insect hosts establish an intimate metabolic relationship. Bacteria offer a variety of essential nutrients to their hosts, whereas insect cells provide the necessary sources of matter and energy to their tiny metabolic allies. These nutritional complementations sustain themselves on a diversity of metabolite exchanges between the cell host and the reduced yet highly specialized bacterial metabolism -which, for instance, overproduces a small set of essential amino acids and vitamins. A well-known case of metabolic complementation is provided by the cedar aphid Cinara cedri that harbors two co-primary endosymbionts, Buchnera aphidicola BCc and Ca. Serratia symbiotica SCc, and in which some metabolic pathways are partitioned between different partners. Here we present a genome scale metabolic network (GEM) for the bacterial consortium from the cedar aphid iBSCc. The analysis of this GEM allows us the confirmation of cases of metabolic complementation previously described by genome analysis (i.e. tryptophan and biotin biosynthesis) and the proposal of a hitherto unnoticed event of metabolic pathway sharing between the two endosymbionts, namely the biosynthesis of tetrahydrofolate. In silico knock-out experiments with iBSCc showed that the consortium metabolism is a highly integrated yet fragile network. We also have explored the evolutionary pathways leading to the emergence of metabolic complementation between reduced metabolisms starting from individual, complete networks. Our results suggest that, during the establishment of metabolic complementation in endosymbionts, adaptive evolution is more significant than previously thought.

systems biology↗