NeMeSys: a biological resource for narrowing the gap between sequence and function in the human pathogen Neisseria meningitidis.
BACKGROUND
Genome sequences, now available for most pathogens, hold promise for the rational design of new therapies. However, biological resources for genome-scale identification of gene function (notably genes involved in pathogenesis) and/or genes essential for cell viability, which are necessary to achieve this goal, are often sorely lacking. This holds true for Neisseria meningitidis, one of the most feared human bacterial pathogens that causes meningitis and septicemia.


RESULTS
By determining and manually annotating the complete genome sequence of a serogroup C clinical isolate of N. meningitidis (strain 8013) and assembling a library of defined mutants in up to 60% of its non-essential genes, we have created NeMeSys, a biological resource for Neisseria meningitidis systematic functional analysis. To further enhance the versatility of this toolbox, we have manually (re)annotated eight publicly available Neisseria genome sequences and stored all these data in a publicly accessible online database. The potential of NeMeSys for narrowing the gap between sequence and function is illustrated in several ways, notably by performing a functional genomics analysis of the biogenesis of type IV pili, one of the most widespread virulence factors in bacteria, and by identifying through comparative genomics a complete biochemical pathway (for sulfur metabolism) that may potentially be important for nasopharyngeal colonization.


CONCLUSIONS
By improving our capacity to understand gene function in an important human pathogen, NeMeSys is expected to contribute to the ongoing efforts aimed at understanding a prokaryotic cell comprehensively and eventually to the design of new therapies.
Rusniok
Christophe
C
Génomique des Microorganismes Pathogènes, Institut Pasteur, rue du Dr Roux, Paris 75015, France. rusniok@pasteur.fr
Vallenet
David
D
Floquet
Stéphanie
S
Ewles
Helen
H
Mouzé-Soulama
Coralie
C
Brown
Daniel
D
Lajus
Aurélie
A
Buchrieser
Carmen
C
Médigue
Claudine
C
Glaser
Philippe
P
Pelicic
Vladimir
V
D001426:Bacterial Proteins / Q000378:metabolism; D001483:Base Sequence; D015169:Colony Count, Microbial; D004251:DNA Transposable Elements / Q000235:genetics; D005455:Fluorescent Antibody Technique; D005798:Genes, Bacterial / Q000235:genetics; D023281:Genomics; D006801:Humans; D050296:Microbial Viability / Q000235:genetics; D005810:Multigene Family; D009154:Mutation / Q000235:genetics; D009305:Nasopharynx / Q000382:microbiology; D009345:Neisseria meningitidis / Q000166:cytology / Q000235:genetics* / Q000472:pathogenicity*; D017422:Sequence Analysis, DNA / Q000379:methods*; D012689:Sequence Homology, Nucleic Acid; D012984:Software; D014774:Virulence / Q000235:genetics
D001426:Bacterial Proteins; D004251:DNA Transposable Elements