19th International CODATA Conference
Category: Knowledge Discovery
Toward the virtual cell genome-based design of a cell-free culture medium for intracellular parasite, Tropheryma whipplei
H. Ogata, P. Renesto, D.
Raoult., JM. Claverie (Jean-Michel.Claverie@igs.cnrs-mrs.fr)
Structural & Genomic Information
Laboratory,
Empirical approaches have guided the development of bacterial cultures. The
availability of sequenced genomes now provides opportunities to define culture
media for growth of fastidious pathogens with computer modeling of metabolic
networks. A key issue is the possibility of growing host-dependent bacteria
in cell-free conditions. The genome sequence of Tropheryma
whipplei, an actinobacteria
causative of Whipple's disease, was analyzed to identify specific metabolic
deficiencies. This evidenced the impossibility for the bacteria to synthesize
a variety of amino acids. We used this information to design a comprehensive
medium that allowed three established T. whipplei
strains from culture with human cells and one new strain from a clinical sample
to grow axenically, that is independently from any cellular host. Genomic information
can, therefore, provide sufficient clues for designing cell-free media for fastidious
and uncultured pathogens. In addition to breaking the rigid classification between
"parasitic" and "free-living" microorganisms, this work
can also be considered a first tangible and useful achievement of in silico
"system" biology. The automatization of
our approach constitutes a possible pathway towards the reification of the "virtual
cell" concept. Methods to automatically generate qualitative Petri net
models from genomic annotation are being explored. References: Lancet 362:447-9
(2003); Science 302, 19-20 (2003).