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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
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Mendum, Tom A., Newcombe, Jane, Mannan, Ahmad A., Kierzek, Andrzej M. and McFadden, Johnjoe (2011) Interrogation of global mutagenesis data with a genome scale model of Neisseria meningitidis to assess gene fitness in vitro and in sera. Genome Biology, 12 . R127. doi:10.1186/gb-2011-12-12-r127 ISSN 1474-760X.
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WRAP-interrogation-global-mutagenesis-data-genome-gene-sera-Mannan-2011.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution 2.0.. Download (1027Kb) | Preview |
Official URL: https://doi.org/10.1186/gb-2011-12-12-r127
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 pathogen's 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 pathogen's metabolism both in vitro and during infection.
| Item Type: | Journal Article | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| Subjects: | Q Science > QR Microbiology | ||||||||
| Divisions: | Faculty of Science, Engineering and Medicine > Engineering > Engineering | ||||||||
| Library of Congress Subject Headings (LCSH): | Neisseria meningitidis -- Genetics, Neisseria meningitidis -- Prevention | ||||||||
| Journal or Publication Title: | Genome Biology | ||||||||
| Publisher: | BioMed Central Ltd. | ||||||||
| ISSN: | 1474-760X | ||||||||
| Official Date: | 30 December 2011 | ||||||||
| Dates: |
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| Volume: | 12 | ||||||||
| Article Number: | R127 | ||||||||
| DOI: | 10.1186/gb-2011-12-12-r127 | ||||||||
| Status: | Peer Reviewed | ||||||||
| Publication Status: | Published | ||||||||
| Access rights to Published version: | Open Access (Creative Commons) | ||||||||
| Date of first compliant deposit: | 1 June 2018 | ||||||||
| Date of first compliant Open Access: | 4 June 2018 | ||||||||
| Open Access Version: |
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