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Interrogation of global mutagenesis data with a genome scale model of Neisseria meningitidis to assess gene fitness in vitro and in sera.

Title: Interrogation of global mutagenesis data with a genome scale model of Neisseria meningitidis to assess gene fitness in vitro and in sera.
Authors: Mendum, TA
Newcombe, J
Mannan, AA
Kierzek, AM
McFadden, J
Item Type: Journal Article
Abstract: BACKGROUND: Neisseria meningitidis is an important human commensal and pathogen that causes several thousand deaths each year, mostly in young children. How the pathogen replicates and causes disease in the host is largely unknown, particularly the role of metabolism in colonization and disease. Completed genome sequences are available for several strains but our understanding of how these data relate to phenotype remains limited. RESULTS: To investigate the metabolism of N. meningitidis we generated and then selected a representative Tn5 library on rich medium, a minimal defined medium and in human serum to identify genes essential for growth under these conditions. To relate these data to a systems-wide understanding of the pathogens biology we constructed a genome-scale metabolic network: Nmb_iTM560. This model was able to distinguish essential and non-essential genes as predicted by the global mutagenesis. These essentiality data, the library and the Nmb_iTM560 model are powerful and widely applicable resources for the study of meningococcal metabolism and physiology. We demonstrate the utility of these resources by predicting and demonstrating metabolic requirements on minimal medium, such as a requirement for phosphoenolpyruvate carboxylase, and by describing the nutritional and biochemical status of N. meningitidis when grown in serum, including a requirement for both the synthesis and transport of amino acids. CONCLUSIONS: This study describes the application of a genome scale transposon library combined with an experimentally validated genome-scale metabolic network of N. meningitidis to identify essential genes and provide novel insight into the pathogens metabolism both in vitro and during infection.
Issue Date: 30-Dec-2011
Date of Acceptance: 30-Dec-2011
URI: http://hdl.handle.net/10044/1/26893
DOI: https://dx.doi.org/10.1186/gb-2011-12-12-r127
ISSN: 1474-760X
Publisher: BioMed Central
Journal / Book Title: Genome Biology
Volume: 12
Issue: R127
Copyright Statement: © 2011 Mendum et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: Amino Acids
Base Sequence
Child
DNA Transposable Elements
Gene Library
Genes, Essential
Genetic Fitness
Genome, Bacterial
Humans
Metabolic Networks and Pathways
Mutagenesis
Neisseria meningitidis
Phosphoenolpyruvate Carboxylase
Serum
Publication Status: Published
Appears in Collections:Mathematics
Applied Mathematics and Mathematical Physics
Faculty of Natural Sciences



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