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.
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Inst Syst Biol, North Seattle, WA 98109 USA
Univ Luxembourg, Luxembourg Ctr Syst Biomed, L-4362 Esch Sur Alzette, LuxembourgInst Syst Biol, North Seattle, WA 98109 USA
Simeonidis, Evangelos
Price, Nathan D.
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Inst Syst Biol, North Seattle, WA 98109 USAInst Syst Biol, North Seattle, WA 98109 USA
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CNRS, LPTMS, F-91405 Orsay, France
Univ Paris 11, UMR8626, Orsay, France
Univ Paris Sud, INRA, Genet Vegetale UMR0320 UMR8120, Gif Sur Yvette, FranceCNRS, LPTMS, F-91405 Orsay, France
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Univ Michigan, Dept Biomed Engn, Ann Arbor, MI 48109 USAUniv Michigan, Dept Biomed Engn, Ann Arbor, MI 48109 USA
Shen, Fangzhou
Boccuto, Luigi
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Greenwood Genet Ctr, Greenwood, SC 29646 USAUniv Michigan, Dept Biomed Engn, Ann Arbor, MI 48109 USA
Boccuto, Luigi
Pauly, Rini
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Greenwood Genet Ctr, Greenwood, SC 29646 USAUniv Michigan, Dept Biomed Engn, Ann Arbor, MI 48109 USA
Pauly, Rini
Srikanth, Sujata
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Greenwood Genet Ctr, Greenwood, SC 29646 USAUniv Michigan, Dept Biomed Engn, Ann Arbor, MI 48109 USA
Srikanth, Sujata
Chandrasekaran, Sriram
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Univ Michigan, Dept Biomed Engn, Ann Arbor, MI 48109 USA
Univ Michigan, Ctr Computat Med & Bioinformat, Ann Arbor, MI 48109 USA
Univ Michigan, Rogel Canc Ctr, Ann Arbor, MI 48109 USAUniv Michigan, Dept Biomed Engn, Ann Arbor, MI 48109 USA
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KTH Royal Inst Technol, Sci Life Lab, Stockholm, SwedenKTH Royal Inst Technol, Sci Life Lab, Stockholm, Sweden
Zhang, Cheng
Aldrees, Mohammed
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King Abdullah Int Med Res Ctr, Dept Med Genom, Riyadh, Saudi Arabia
King Saud Bin Abdul Aziz Univ Hlth Sci, Riyadh, Saudi Arabia
Minist Natl Guard Hlth Affairs, Riyadh, Saudi ArabiaKTH Royal Inst Technol, Sci Life Lab, Stockholm, Sweden
Aldrees, Mohammed
Arif, Muhammad
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KTH Royal Inst Technol, Sci Life Lab, Stockholm, SwedenKTH Royal Inst Technol, Sci Life Lab, Stockholm, Sweden
Arif, Muhammad
Li, Xiangyu
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KTH Royal Inst Technol, Sci Life Lab, Stockholm, SwedenKTH Royal Inst Technol, Sci Life Lab, Stockholm, Sweden
Li, Xiangyu
Mardinoglu, Adil
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KTH Royal Inst Technol, Sci Life Lab, Stockholm, Sweden
Chalmers Univ Technol, Dept Biol & Biol Engn, Gothenburg, Sweden
Kings Coll London, Ctr Host Microbiome Interact, Dent Inst, London, EnglandKTH Royal Inst Technol, Sci Life Lab, Stockholm, Sweden
Mardinoglu, Adil
Aziz, Mohammad Azhar
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King Saud Bin Abdul Aziz Univ Hlth Sci, Riyadh, Saudi Arabia
Minist Natl Guard Hlth Affairs, Riyadh, Saudi Arabia
King Abdullah Int Med Res Ctr, Colorectal Canc Res Program, Riyadh, Saudi ArabiaKTH Royal Inst Technol, Sci Life Lab, Stockholm, Sweden