原创力文档interrogation of global mutagenesis data with a genome scale model of neisseria meningitidis to assess gene fitness in vitro and in sera审讯的全球诱变数据与脑膜炎奈瑟菌的基因组规模模型来评估基因健身体外和血清.pdfVIP
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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审讯的全球诱变数据与脑膜炎奈瑟菌的基因组规模模型来评估基因健身体外和血清
Mendum et al. Genome Biology 2011, 12:R127
/2012/12/12/R127
RESEARCH Open Access
Interrogation of global mutagenesis data with a
genome scale model of Neisseria meningitidis to
assess gene fitness in vitro and in sera
*
Tom A Mendum, Jane Newcombe, Ahmad A Mannan, Andrzej M Kierzek and Johnjoe McFadden
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 synt
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