Research

NeMeSys: a biological resource for narrowing the gap between sequence and function in the human pathogen Neisseria meningitidis

Christophe Rusniok^1,5†, David Vallenet^2†, Stéphanie Floquet^3,6, Helen Ewles⁴, Coralie Mouzé-Soulama^3,7, Daniel Brown⁴, Aurélie Lajus², Carmen Buchrieser^1,5, Claudine Médigue², Philippe Glaser¹ and Vladimir Pelicic^3,4*

• * Corresponding author: Vladimir Pelicic v.pelicic@imperial.ac.uk

• † Equal contributors

Author Affiliations

¹ Génomique des Microorganismes Pathogènes, Institut Pasteur, rue du Dr Roux, Paris, 75015, France

² Génomique Métabolique, CNRS UMR8030, Laboratoire de Génomique Comparative, CEA-Institut de Génomique-Génoscope, rue Gaston Crémieux, Evry, 91057, France

³ U570 INSERM, Faculté de Médecine René Descartes-Paris 5, rue de Vaugirard, Paris, 75015, France

⁴ Department of Microbiology, CMMI, Imperial College London, Armstrong Road, London, SW7 2AZ, UK

⁵ Current address: Biologie des Bactéries Intracellulaires, Institut Pasteur, rue du Dr Roux, Paris, 75015, France

⁶ Current address: Mutabilis, Parc Biocitech, avenue Gaston Roussel, Romainville, 93230, France

⁷ Current address: FAB pharma, rue Saint Honoré, Paris, 75001, France

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Genome Biology 2009, 10:R110 doi:10.1186/gb-2009-10-10-r110

Published: 9 October 2009

Abstract

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.