A curated genome-scale metabolic model of Bordetella pertussis metabolism

被引:8
|
作者
Fyson, Nick [1 ]
King, Jerry [2 ,3 ]
Belcher, Thomas [2 ,3 ]
Preston, Andrew [2 ,3 ]
Colijn, Caroline [1 ]
机构
[1] Imperial Coll, Dept Math, London, England
[2] Univ Bath, Milner Ctr Evolut, Bath, Avon, England
[3] Univ Bath, Dept Biol & Biochem, Bath, Avon, England
基金
英国工程与自然科学研究理事会; 英国生物技术与生命科学研究理事会;
关键词
ESCHERICHIA-COLI; TOXIN; RECONSTRUCTION; CULTIVATION; EXPRESSION; PHENOTYPES;
D O I
10.1371/journal.pcbi.1005639
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
The Gram-negative bacterium Bordetella pertussis is the causative agent of whooping cough, a serious respiratory infection causing hundreds of thousands of deaths annually worldwide. There are effective vaccines, but their production requires growing large quantities of B. pertussis. Unfortunately, B. pertussis has relatively slow growth in culture, with low biomass yields and variable growth characteristics. B. pertussis also requires a relatively expensive growth medium. We present a new, curated flux balance analysis-based model of B. pertussis metabolism. We enhance the model with an experimentally-determined biomass objective function, and we perform extensive manual curation. We test the model's predictions with a genome-wide screen for essential genes using a transposon-directed insertional sequencing (TraDIS) approach. We test its predictions of growth for different carbon sources in the medium. The model predicts essentiality with an accuracy of 83% and correctly predicts improvements in growth under increased glutamate: fumarate ratios. We provide the model in SBML format, along with gene essentiality predictions.
引用
收藏
页数:17
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