TY - JOUR A1 - Botero, David A1 - Monk, Jonathan A1 - Rodriguez Cubillos, Maria Juliana A1 - Rodriguez Cubillos, Andres Eduardo A1 - Restrepo, Mariana A1 - Bernal-Galeano, Vivian A1 - Reyes, Alejandro A1 - Gonzalez Barrios, Andres A1 - Palsson, Bernhard O. A1 - Restrepo, Silvia A1 - Bernal, Adriana T1 - Genome-scale metabolic model of Xanthomonas phaseoli pv. manihotis BT - an approach to elucidate pathogenicity at the metabolic level JF - Frontiers in genetics N2 - Xanthomonas phaseoli pv. manihotis (Xpm) is the causal agent of cassava bacterial blight, the most important bacterial disease in this crop. There is a paucity of knowledge about the metabolism of Xanthomonas and its relevance in the pathogenic process, with the exception of the elucidation of the xanthan biosynthesis route. Here we report the reconstruction of the genome-scale model of Xpm metabolism and the insights it provides into plant-pathogen interactions. The model, iXpm1556, displayed 1,556 reactions, 1,527 compounds, and 890 genes. Metabolic maps of central amino acid and carbohydrate metabolism, as well as xanthan biosynthesis of Xpm, were reconstructed using Escher (https://escher.github.io/) to guide the curation process and for further analyses. The model was constrained using the RNA-seq data of a mutant of Xpm for quorum sensing (QS), and these data were used to construct context-specific models (CSMs) of the metabolism of the two strains (wild type and QS mutant). The CSMs and flux balance analysis were used to get insights into pathogenicity, xanthan biosynthesis, and QS mechanisms. Between the CSMs, 653 reactions were shared; unique reactions belong to purine, pyrimidine, and amino acid metabolism. Alternative objective functions were used to demonstrate a trade-off between xanthan biosynthesis and growth and the re-allocation of resources in the process of biosynthesis. Important features altered by QS included carbohydrate metabolism, NAD(P)(+) balance, and fatty acid elongation. In this work, we modeled the xanthan biosynthesis and the QS process and their impact on the metabolism of the bacterium. This model will be useful for researchers studying host-pathogen interactions and will provide insights into the mechanisms of infection used by this and other Xanthomonas species. KW - Xanthomonas KW - Xpm KW - cassava bacterial blight KW - genome-scale metabolic KW - model KW - quorum sensing Y1 - 2020 U6 - https://doi.org/10.3389/fgene.2020.00837 SN - 1664-8021 VL - 11 PB - Frontiers Media CY - Lausanne ER - TY - JOUR A1 - Fernandez-Nino, Miguel A1 - Giraldo, Daniel A1 - Lucia Gomez-Porras, Judith A1 - Dreyer, Ingo A1 - Gonzalez Barrios, Andres Fernando A1 - Arevalo-Ferro, Catalina T1 - A synthetic multi-cellular network of coupled self-sustained oscillators JF - PLoS one N2 - Engineering artificial networks from modular components is a major challenge in synthetic biology. In the past years, single units, such as switches and oscillators, were successfully constructed and implemented. The effective integration of these parts into functional artificial self-regulated networks is currently on the verge of breakthrough. Here, we describe the design of a modular higher-order synthetic genetic network assembled from two independent self-sustained synthetic units: repressilators coupled via a modified quorum-sensing circuit. The isolated communication circuit and the network of coupled oscillators were analysed in mathematical modelling and experimental approaches. We monitored clustering of cells in groups of various sizes. Within each cluster of cells, cells oscillate synchronously, whereas the theoretical modelling predicts complete synchronization of the whole cellular population to be obtained approximately after 30 days. Our data suggest that self-regulated synchronization in biological systems can occur through an intermediate, long term clustering phase. The proposed artificial multicellular network provides a system framework for exploring how a given network generates a specific behaviour. Y1 - 2017 U6 - https://doi.org/10.1371/journal.pone.0180155 SN - 1932-6203 VL - 12 PB - PLoS CY - San Fransisco ER -