Model-driven design allows growth of Mycoplasma pneumoniae on serum-free media

Autor: Erika Gaspari, Luis Garcia-Morales, Luis Serrano, Maria Suarez-Diez, Antoni Malachowski, Vitor A. P. Martins dos Santos, Raul Burgos
Přispěvatelé: Laboratory of Systems and Synthetic Biology, Wageningen University and Research [Wageningen] (WUR), Biologie du fruit et pathologie (BFP), Université de Bordeaux (UB)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), The Barcelona Institute for Science and Technology [Barcelona, Spain], This work has received funding from European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program under grant agreement no. 634942 (MycoSynVac) and no. 670216 (MYCOCHASSIS)., European Project: 634942,H2020,H2020-LEIT-BIO-2014-1,MycoSynVac(2015), European Project: 670216,H2020,ERC-2014-ADG,MYCOCHASSIS(2015)
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Mycoplasma pneumoniae
[SDV]Life Sciences [q-bio]
Human pathogen
Computational biology
Biology
Bacterial growth
medicine.disease_cause
Models
Biological

General Biochemistry
Genetics and Molecular Biology

Culture Media
Serum-Free

Article
Metabolic engineering
Cell membrane
03 medical and health sciences
Drug Discovery
medicine
Life Science
Systems and Synthetic Biology
lcsh:QH301-705.5
VLAG
030304 developmental biology
Systeem en Synthetische Biologie
0303 health sciences
[SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health
Biochemical networks
030306 microbiology
Applied Mathematics
030302 biochemistry & molecular biology
Lipid metabolism
biology.organism_classification
Computer Science Applications
Computational biology and bioinformatics
Vaccination
Chemically defined medium
medicine.anatomical_structure
lcsh:Biology (General)
Modeling and Simulation
Computer modelling
Energy Metabolism
Glycolysis
Bacteria
[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Zdroj: npj Systems Biology and Applications
npj Systems Biology and Applications, 2020, 6 (1), pp.33. ⟨10.1038/s41540-020-00153-7⟩
npj Systems Biology and Applications, Nature Research, 2020, 6 (1), pp.33. ⟨10.1038/s41540-020-00153-7⟩
npj Systems Biology and Applications, Vol 6, Iss 1, Pp 1-11 (2020)
npj Systems Biology and Applications 6 (2020)
NPJ Systems Biology and Applications
npj Systems Biology and Applications, 6
ISSN: 2056-7189
DOI: 10.1038/s41540-020-00153-7⟩
Popis: Mycoplasma pneumoniaeis a slow-growing, human pathogen that causes atypical pneumonia. Because it lacks a cell wall, many antibiotics are ineffective, and vaccination is required. Due to its reduced genome and dearth of many biosynthetic pathways, this fastidious bacterium depends on rich, undefined medium for growth, which makes large-scale cultivation for vaccine production challenging and expensive.To understand factors limiting growth, we developed a genome-scale, constraint-based model ofM. pneumoniaecalled iEG158_mpn to describe the metabolic potential of this bacterium. We have put special emphasis on cell membrane formation to identify key lipid components to maximize bacterial growth. We have used this knowledge to predict and validatein vitrotwo serum-free media able to sustain growth.Our findings also show that glycolysis and lipid metabolism are much less efficient under hypoxia; these findings suggest that factors other than metabolism and membrane formation alone affect the growth ofM. pneumoniae.Altogether, our modelling approach enabled us to optimize medium composition, capacitated growth in defined media and streamlined operational requirements, thereby providing the basis for stable, reproducible and less expensive vaccine production.
Databáze: OpenAIRE