Metabolic modeling of a mutualistic microbial community.
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ABSTRACT:
SUBMITTER: Stolyar S
PROVIDER: S-EPMC1847946 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Metabolic network modeling of microbial communities provides an in-depth understanding of community-wide metabolic and regulatory processes. Compared to single organism analyses, community metabolic network modeling is more complex because it needs to account for interspecies interactions. To date, most approaches focus on reconstruction of high-quality individual networks so that, when combined, they can predict community behaviors as a result of interspecies interactions. However, this conventional method becomes ineffective for communities whose members are not well characterized and cannot be experimentally interrogated in isolation. Here, we tested a new approach that uses community-level data as a critical input for the network reconstruction process. This method focuses on directly predicting interspecies metabolic interactions in a community, when axenic information is insufficient. We validated our method through the case study of a bacterial photoautotroph-heterotroph consortium that was used to provide data needed for a community-level metabolic network reconstruction. Resulting simulations provided experimentally validated predictions of how a photoautotrophic cyanobacterium supports the growth of an obligate heterotrophic species by providing organic carbon and nitrogen sources. J. Cell. Physiol. 231: 2339-2345, 2016. © 2016 Wiley Periodicals, Inc.
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Project description:In nature, microbes do not exist in isolation but co-exist in a variety of ecological and biological environments and on various host organisms. Due to their close proximity, these microbes interact among themselves, and also with the hosts in both positive and negative manners. Moreover, these interactions may modulate dynamically upon external stimulus as well as internal community changes. This demands systematic techniques such as mathematical modeling to understand the intrinsic community behavior. Here, we reviewed various approaches for metabolic modeling of microbial communities. If detailed species-specific information is available, segregated models of individual organisms can be constructed and connected via metabolite exchanges; otherwise, the community may be represented as a lumped network of metabolic reactions. The constructed models can then be simulated to help fill knowledge gaps, and generate testable hypotheses for designing new experiments. More importantly, such community models have been developed to study microbial interactions in various niches such as host microbiome, biogeochemical and bioremediation, waste water treatment and synthetic consortia. As such, the metabolic modeling efforts have allowed us to gain new insights into the natural and synthetic microbial communities, and design interventions to achieve specific goals. Finally, potential directions for future development in metabolic modeling of microbial communities were also discussed.
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Project description:BackgroundThe role of methane in global warming has become paramount to the environment and the human society, especially in the past few decades. Methane cycling microbial communities play an important role in the global methane cycle, which is why the characterization of these communities is critical to understand and manipulate their behavior. Methanotrophs are a major player in these communities and are able to oxidize methane as their primary carbon source.ResultsLake Washington is a freshwater lake characterized by a methane-oxygen countergradient that contains a methane cycling microbial community. Methanotrophs are a major part of this community involved in assimilating methane from lake water. Two significant methanotrophic species in this community are Methylobacter and Methylomonas. In this work, these methanotrophs are computationally studied via developing highly curated genome-scale metabolic models. Each model was then integrated to form a community model with a multi-level optimization framework. The competitive and mutualistic metabolic interactions among Methylobacter and Methylomonas were also characterized. The community model was next tested under carbon, oxygen, and nitrogen limited conditions in addition to a nutrient-rich condition to observe the systematic shifts in the internal metabolic pathways and extracellular metabolite exchanges. Each condition showed variations in the methane oxidation pathway, pyruvate metabolism, and the TCA cycle as well as the excretion of formaldehyde and carbon di-oxide in the community. Finally, the community model was simulated under fixed ratios of these two members to reflect the opposing behavior in the two-member synthetic community and in sediment-incubated communities. The community simulations predicted a noticeable switch in intracellular carbon metabolism and formaldehyde transfer between community members in sediment-incubated vs. synthetic condition.ConclusionIn this work, we attempted to predict the response of a simplified methane cycling microbial community from Lake Washington to varying environments and also provide an insight into the difference of dynamics in sediment-incubated microcosm community and synthetic co-cultures. Overall, this study lays the ground for in silico systems-level studies of freshwater lake ecosystems, which can drive future efforts of understanding, engineering, and modifying these communities for dealing with global warming issues.
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Project description:Manipulating the rhizosphere microbial community through beneficial microorganism inoculation has gained interest in improving crop productivity and stress resistance. Synthetic microbial communities, known as SynComs, mimic natural microbial compositions while reducing the number of components. However, achieving this goal requires a comprehensive understanding of natural microbial communities and carefully selecting compatible microorganisms with colonization traits, which still pose challenges. In this study, we employed multi-genome metabolic modeling of 270 previously described metagenome-assembled genomes from Campos rupestres to design a synthetic microbial community to improve the yield of important crop plants. We used a targeted approach to select a minimal community (MinCom) encompassing essential compounds for microbial metabolism and compounds relevant to plant interactions. This resulted in a reduction of the initial community size by approximately 4.5-fold. Notably, the MinCom retained crucial genes associated with essential plant growth-promoting traits, such as iron acquisition, exopolysaccharide production, potassium solubilization, nitrogen fixation, GABA production, and IAA-related tryptophan metabolism. Furthermore, our in-silico selection for the SymComs, based on a comprehensive understanding of microbe-microbe-plant interactions, yielded a set of six hub species that displayed notable taxonomic novelty, including members of the Eremiobacterota and Verrucomicrobiota phyla. Overall, the study contributes to the growing body of research on synthetic microbial communities and their potential to enhance agricultural practices. The insights gained from our in-silico approach and the selection of hub species pave the way for further investigations into the development of tailored microbial communities that can optimize crop productivity and improve stress resilience in agricultural systems.
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Project description:Mutualisms can be promoted by pleiotropic win-win mutations which directly benefit self (self-serving) and partner (partner-serving). Intuitively, partner-serving phenotype could be quantified as an individual's benefit supply rate to partners. Here, we demonstrate the inadequacy of this thinking, and propose an alternative. Specifically, we evolved well-mixed mutualistic communities where two engineered yeast strains exchanged essential metabolites lysine and hypoxanthine. Among cells that consumed lysine and released hypoxanthine, a chromosome duplication mutation seemed win-win: it improved cell's affinity for lysine (self-serving), and increased hypoxanthine release rate per cell (partner-serving). However, increased release rate was due to increased cell size accompanied by increased lysine utilization per birth. Consequently, total hypoxanthine release rate per lysine utilization (defined as 'exchange ratio') remained unchanged. Indeed, this mutation did not increase the steady state growth rate of partner, and is thus solely self-serving during long-term growth. By extension, reduced benefit production rate by an individual may not imply cheating.
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Project description:AIMS:To identify putative mutualistic interactions driving community composition in polymicrobial chronic wound infections using metabolic modelling. METHODS AND RESULTS:We developed a 12 species metabolic model that covered 74% of 16S rDNA pyrosequencing reads of dominant genera from 2963 chronic wound patients. The community model was used to predict species abundances averaged across this large patient population. We found that substantially improved predictions were obtained when the model was constrained with genera prevalence data and predicted abundances were averaged over 5000 ensemble simulations with community participants randomly determined according to the experimentally determined prevalences. Staphylococcus and Pseudomonas were predicted to exhibit a strong mutualistic relationship that resulted in community growth rate and diversity simultaneously increasing, suggesting that these two common chronic wound pathogens establish dominance by cooperating with less harmful commensal species. In communities lacking one or both dominant pathogens, other mutualistic relationship including Staphylococcus/Acinetobacter, Pseudomonas/Serratia and Streptococcus/Enterococcus were predicted consistent with published experimental data. CONCLUSIONS:Mutualistic interactions were predicted to be driven by crossfeeding of organic acids, alcohols and amino acids that could potentially be disrupted to slow chronic wound disease progression. SIGNIFICANCE AND IMPACT OF THE STUDY:Approximately 2% of the US population suffers from nonhealing chronic wounds infected by a combination of commensal and pathogenic bacteria. These polymicrobial infections are often resilient to antibiotic treatment due to the nutrient-rich wound environment and species interactions that promote community stability and robustness. The simulation results from this study were used to identify putative mutualistic interactions between bacteria that could be targeted to enhance treatment efficacy.
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Project description:Obesity is a risk factor for colorectal cancer (CRC), and the involvement of gut microbiota in the pathogenesis of obesity and CRC is widely recognized. However, the landscape of fecal microbiome and metabolome distinguishing patients with obesity-related CRC from obesity remains unknown. Here, we utilize metagenomic sequencing and metabolomics from 522 patients with CRC and healthy controls to identify the characteristics of obese CRC. Our integrated analysis reveals that obesity-related CRC is characterized by elevated Peptostreptococcus stomatis, dysregulated fatty acids and phospholipids, and altered Kyoto Encyclopedia of Genes and Genomes pathways involving glycerophospholipid metabolism and lipopolysaccharide synthesis. Correlation analysis unveils microbial interactions in obesity, where the probiotic Faecalibacterium prausnitzii and the tumor-promoting species P. stomatis may engage in cross-feeding, thereby promoting tumorigenesis. In vitro experiments affirm enhanced growth under cross-feeding conditions. The mutualistic microbe-microbe interaction may contribute to the association between obesity and elevated CRC risk. Additionally, diagnostic models incorporating BMI-specific microbial biomarkers display promise for precise CRC screening.
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