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

Abstract

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.

How clonal are Neisseria species? The epidemic clonality model revisited

“…5, because this study considered only strains with different genotypes. There also is a strong parity between MLST diversity on one hand and the data revealed by microarrays (29,32) and WGS (12) on the other hand. In contrast to the sample surveyed in ref.…”

“…However, (i) the persistence of some near-clades since 1917 and 1930 (7) far exceeds this duration; (ii) again, it would not be expected that the survival of the same CCs would be maintained mainly by natural selection for so long and in so many different environments; (iii) the two near-clades revealed within 83 serogroup A strains (31) do not fit the epidemic clonality model, because a strong LD persists within each of them, although no repeated genotypes are recorded in this sample. More importantly, the two microarray studies (29,32), which are not limited to the serogroup A and which include both carriage and pathogenic strains, do evidence a strong and persistent population structure. Such a structure based on so many different markers strongly suggests the existence of deep phylogenies.…”

“…Many examples of N. meningitidis MLGs that spread over continents and persist for decades are available (13,14,28,32). For example, ET 19 has been sampled from 1967-1983 in 14 different countries and several continents, and ET 48 has been recorded from 1969-1989 in eight different countries (30).…”

“…This condition shows that these two near-clades each undergo PCE and hence cannot be equated with cryptic biological species. In the two microarray studies (29,32), the two main genetic groups are further distributed into eight lesser genome groups. This sample corresponds to 22 different CCs that correspond to the genome groups.…”

Post-genomics ofNeisseria meningitidis: an update

“…In a study by Hotopp et al, the authors developed a microarray platform containing the predicted genes of MenB strain MC58, plus the unique genetic region of MenA strain Z2491, MenC strain FAm18 and Neisseria gonorrhoeae FA1090 [20]. This platform was used to perform large CGH studies on numerous neisserial isolates (one Neisseria cinerea, two N. lactamica, two N. gonorrhoeae and 48 N. meningitidis isolates).…”