Constraint-based analysis of metabolic capacity of Salmonella typhimurium during host-pathogen interaction

Raghunathan, Anu; Reed, Jennifer L.; Shin, Sook-il; Palsson, Bernhard Ø.; Daefler, Simon

doi:10.1186/1752-0509-3-38

Cited by 146 publications

(163 citation statements)

References 63 publications

(80 reference statements)

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“…S1 in the supplemental material). Biomass requirements were also based on the previously reported S. enterica biomass composition and biomass-viable-cell conversion factor under aerobic conditions (31,32). The relative sufficiency of each amino acid was expressed as the ratio between the biomass requirement and the availability in alfalfa exudates (see Table S6 in the supplemental material).…”

Section: Resultsmentioning

confidence: 99%

“…However, a moderate correlation (Pearson's R 2 ϭ 0.45; P ϭ 0.01) was discovered between the perceived sufficiency of amino acids and the amino acid auxotrophs' growth phenotypes. The perceived sufficiency of each amino acid was expressed as a ratio of the calculated biomass requirement (based on the S. enterica growth curve observed in association with roots and the biomass equation [32]) to the available concentration. This ratio is a novel approach to evaluating the nutritional status and allows the prediction of nutrients that may be limiting for bacterial growth.…”

Section: Discussionmentioning

confidence: 99%

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De Novo Amino Acid Biosynthesis Contributes to Salmonella enterica Growth in Alfalfa Seedling Exudates

Kwan

Pisithkul

Amador‐Noguez

et al. 2015

Appl Environ Microbiol

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Salmonella enterica is a member of the plant microbiome. Growth of S. enterica in sprouting-seed exudates is rapid; however, the active metabolic networks essential in this environment are unknown. To examine the metabolic requirements of S. enterica during growth in sprouting-seed exudates, we inoculated alfalfa seeds and identified 305 S. enterica proteins extracted 24 h postinoculation from planktonic cells. Over half the proteins had known metabolic functions, and they are involved in over onequarter of the known metabolic reactions. Ion and metabolite transport accounted for the majority of detected reactions. Proteins involved in amino acid transport and metabolism were highly represented, suggesting that amino acid metabolic networks may be important for S. enterica growth in association with roots. Amino acid auxotroph growth phenotypes agreed with the proteomic data; auxotrophs in amino acid-biosynthetic pathways that were detected in our screen developed growth defects by 48 h. When the perceived sufficiency of each amino acid was expressed as a ratio of the calculated biomass requirement to the available concentration and compared to growth of each amino acid auxotroph, a correlation between nutrient availability and bacterial growth was found. Furthermore, glutamate transport acted as a fitness factor during S. enterica growth in association with roots. Collectively, these data suggest that S. enterica metabolism is robust in the germinating-alfalfa environment; that single-amino-acid metabolic pathways are important but not essential; and that targeting central metabolic networks, rather than dedicated pathways, may be necessary to achieve dramatic impacts on bacterial growth. P lants can influence both the number and species of bacteria that colonize their surfaces. The availability and types of nutrients, secretion of chemoattractants or repellents, and production of antimicrobial compounds all impact the composition of the plant-associated bacterial community. In particular, germinating seeds and roots release exudates containing complex mixtures of amino acids, sugars, organic acids, and other plant metabolites that support the growth of microbial colonists in the spermosphere and rhizosphere (1-5). Successful colonization of and persistence in these plant niches requires that bacteria acquire and metabolize these plant-derived nutrients and biosynthesize any required metabolites not sufficiently available from the plant.The compositions of seed and root exudates are dynamic and vary based on seed and plant age, soil type, temperature, nutritional status, and crop (6, 7). The identity and quantity of nutrients in plant exudates have a profound impact on bacterial growth and metabolic activity (8). Seeds that released larger quantities of carbohydrates and amino acids supported higher Enterobacter cloacae populations, rates of bacterial growth, and metabolic activity (3,4,8). Nutrient identity (e.g., alanine, arginine, and aspartate), not just type (e.g., amino acids, sugars, and lipids), influen...

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

De Novo Amino Acid Biosynthesis Contributes to Salmonella enterica Growth in Alfalfa Seedling Exudates

Kwan

Pisithkul

Amador‐Noguez

et al. 2015

Appl Environ Microbiol

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“…However, some minor biomass components may be restricted to some organisms and may not be required in others. A potential example is siroheme, a molecule that is part of E. coli biomass but may not be needed in other organisms (46,52,(71)(72)(73). In an organism that does not need this molecule, 1.6% (two reactions) of our absolutely superessential reactions lose this status.…”

Section: Discussionmentioning

confidence: 99%

Superessential reactions in metabolic networks

Barve

Rodrigues²,

Wagner³

2012

Proc. Natl. Acad. Sci. U.S.A.

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The metabolic genotype of an organism can change through loss and acquisition of enzyme-coding genes, while preserving its ability to survive and synthesize biomass in specific environments. This evolutionary plasticity allows pathogens to evolve resistance to antimetabolic drugs by acquiring new metabolic pathways that bypass an enzyme blocked by a drug. We here study quantitatively the extent to which individual metabolic reactions and enzymes can be bypassed. To this end, we use a recently developed computational approach to create large metabolic network ensembles that can synthesize all biomass components in a given environment but contain an otherwise random set of known biochemical reactions. Using this approach, we identify a small connected core of 124 reactions that are absolutely superessential (that is, required in all metabolic networks). Many of these reactions have been experimentally confirmed as essential in different organisms. We also report a superessentiality index for thousands of reactions. This index indicates how easily a reaction can be bypassed. We find that it correlates with the number of sequenced genomes that encode an enzyme for the reaction. Superessentiality can help choose an enzyme as a potential drug target, especially because the index is not highly sensitive to the chemical environment that a pathogen requires. Our work also shows how analyses of large network ensembles can help understand the evolution of complex and robust metabolic networks.drug resistance | drug target identification | essential reactions

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“…Metabolic networks in bacteria; constraint-based modeling One approach to integrate genomic and other omics data to predict system function in micro-organisms is to derive constraint-based genome-scale metabolic models (Joyce and Palsson, 2006;Schuetz et al, 2007;Raghunathan et al, 2009). This is an example of a 'top-down' approach, as the possible ways that a cell could function are inferred from genome-wide data sets.…”

Section: Applications In Systems Biologymentioning

confidence: 99%

“…The constraint-based metabolic model of Salmonella enterica serovar typhimurium reported by Raghunathan et al (2009) contains 1083 genes, 973 proteins, 744 metabolites and 1087 metabolic reactions, of which 1018 are gene associated. Estimates for the metabolite concentrations under the condition of steady state were obtained from literature or from experimental measurements.…”

Section: Systems Biology In Animal Sciencesmentioning

confidence: 99%

Systems biology in animal sciences

Woelders

Pas

Bannink

et al. 2011

Animal

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Systems biology is a rapidly expanding field of research and is applied in a number of biological disciplines. In animal sciences, omics approaches are increasingly used, yielding vast amounts of data, but systems biology approaches to extract understanding from these data of biological processes and animal traits are not yet frequently used. This paper aims to explain what systems biology is and which areas of animal sciences could benefit from systems biology approaches. Systems biology aims to understand whole biological systems working as a unit, rather than investigating their individual components. Therefore, systems biology can be considered a holistic approach, as opposed to reductionism. The recently developed 'omics' technologies enable biological sciences to characterize the molecular components of life with ever increasing speed, yielding vast amounts of data. However, biological functions do not follow from the simple addition of the properties of system components, but rather arise from the dynamic interactions of these components. Systems biology combines statistics, bioinformatics and mathematical modeling to integrate and analyze large amounts of data in order to extract a better understanding of the biology from these huge data sets and to predict the behavior of biological systems. A 'system' approach and mathematical modeling in biological sciences are not new in itself, as they were used in biochemistry, physiology and genetics long before the name systems biology was coined. However, the present combination of mass biological data and of computational and modeling tools is unprecedented and truly represents a major paradigm shift in biology. Significant advances have been made using systems biology approaches, especially in the field of bacterial and eukaryotic cells and in human medicine. Similarly, progress is being made with 'system approaches' in animal sciences, providing exciting opportunities to predict and modulate animal traits.

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Constraint-based analysis of metabolic capacity of Salmonella typhimurium during host-pathogen interaction

Cited by 146 publications

References 63 publications

De Novo Amino Acid Biosynthesis Contributes to Salmonella enterica Growth in Alfalfa Seedling Exudates

De Novo Amino Acid Biosynthesis Contributes to Salmonella enterica Growth in Alfalfa Seedling Exudates

Superessential reactions in metabolic networks

Systems biology in animal sciences

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