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Microbiology 152 (2006), 3733-3749; DOI  10.1099/mic.0.29261-0
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Microbiology 152 (2006), 3733-3749; DOI  10.1099/mic.0.29261-0
© 2006 Society for General Microbiology

Comparative genomics of Neisseria meningitidis: core genome, islands of horizontal transfer and pathogen-specific genes

Julie C. Dunning Hotopp1, Renata Grifantini2, Nikhil Kumar1, Yih Ling Tzeng3, Derrick Fouts1, Elisabetta Frigimelica2, Monia Draghi2,{dagger}, Marzia Monica Giuliani2, Rino Rappuoli2, David S. Stephens3, Guido Grandi2 and Hervé Tettelin1

1 The Institute for Genomic Research, 9712 Medical Center Dr, Rockville, MD 20850, USA
2 Novartis Vaccines and Diagnostics Ltd, Via Fiorentina 1, 53100 Siena, Italy
3 Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia 30322 and Research Service, VA Medical Center, Decatur, GA 30033, USA

Correspondence
Julie C. Dunning Hotopp
jdunning{at}tigr.org

To better understand Neisseria meningitidis genomes and virulence, microarray comparative genome hybridization (mCGH) data were collected from one Neisseria cinerea, two Neisseria lactamica, two Neisseria gonorrhoeae and 48 Neisseria meningitidis isolates. For N. meningitidis, these isolates are from diverse clonal complexes, invasive and carriage strains, and all major serogroups. The microarray platform represented N. meningitidis strains MC58, Z2491 and FAM18, and N. gonorrhoeae FA1090. By comparing hybridization data to genome sequences, the core N. meningitidis genome and insertions/deletions (e.g. capsule locus, type I secretion system) related to pathogenicity were identified, including further characterization of the capsule locus, bioinformatics analysis of a type I secretion system, and identification of some metabolic pathways associated with intracellular survival in pathogens. Hybridization data clustered meningococcal isolates from similar clonal complexes that were distinguished by the differential presence of six distinct islands of horizontal transfer. Several of these islands contained prophage or other mobile elements, including a novel prophage and a transposon carrying portions of a type I secretion system. Acquisition of some genetic islands appears to have occurred in multiple lineages, including transfer between N. lactamica and N. meningitidis. However, island acquisition occurs infrequently, such that the genomic-level relationship is not obscured within clonal complexes. The N. meningitidis genome is characterized by the horizontal acquisition of multiple genetic islands; the study of these islands reveals important sets of genes varying between isolates and likely to be related to pathogenicity.


Abbreviations: IHT, island of horizontal transfer; MLEE, multi-locus enzyme electrophoresis; MLST, multi-locus sequence typing; mCGH, microarray comparative genome hybridization; RMS, restriction/modification system

The ArrayExpress accesssion numbers for the array data related to this paper are A-TIGR-22 and E-TIGR-129.

A supplementary figure and two supplementary tables are available with the online version of this paper.

{dagger}Present address: Departments of Structural Biology and Microbiology and Immunology, Stanford University, School of Medicine, Stanford, CA 94305, USA.




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