Virulence evolution of the human pathogen Neisseria meningitidis by recombination in the core and accessory genome

• Published in: PloS one Vol. 6; no. 4; p. e18441
• Main Authors: Joseph, Biju, Schwarz, Roland F, Linke, Burkhard, Blom, Jochen, Becker, Anke, Claus, Heike, Goesmann, Alexander, Frosch, Matthias, Müller, Tobias, Vogel, Ulrich, Schoen, Christoph
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 26-04-2011; Public Library of Science (PLoS)
• Subjects: Analysis; Bioinformatics; Biology; Biotechnology; Cluster Analysis; Comparative Genomic Hybridization; Computer applications; Deoxyribonucleic acid; Differential distribution; DNA; DNA biosynthesis; DNA microarrays; DNA repair; DNA replication; Epidemics; Evolution; Evolution, Molecular; Evolutionary biology; Gene Pool; Gene sequencing; Gene transfer; Genes; Genetic research; Genome, Bacterial - genetics; Genomes; Genomic islands; Genomics; Health care; Homologous recombination; Homology; Humans; Hybridization; Hygiene; Laboratories; Medical research; Meningitis; Meningococcal disease; Metabolism; Multilocus Sequence Typing; Mutation; Nasopharynx; Neisseria; Neisseria meningitidis; Neisseria meningitidis - classification; Neisseria meningitidis - genetics; Neisseria meningitidis - pathogenicity; Nucleotide sequence; Pathogens; Phylogenetics; Phylogeny; Physiological aspects; Population; Population structure; Prophages; Proteins; Recombination, Genetic - genetics; Secretion; Serotyping; Studies; Vaccines; Virulence; Virulence (Microbiology); Virulence - genetics; Germany
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0018441

Neisseria meningitidis is a naturally transformable, facultative pathogen colonizing the human nasopharynx. Here, we analyze on a genome-wide level the impact of recombination on gene-complement diversity and virulence evolution in N. meningitidis. We combined comparative genome hybridization using microarrays (mCGH) and multilocus sequence typing (MLST) of 29 meningococcal isolates with computational comparison of a subset of seven meningococcal genome sequences.
We found that lateral gene transfer of minimal mobile elements as well as prophages are major forces shaping meningococcal population structure. Extensive gene content comparison revealed novel associations of virulence with genetic elements besides the recently discovered meningococcal disease associated (MDA) island. In particular, we identified an association of virulence with a recently described canonical genomic island termed IHT-E and a differential distribution of genes encoding RTX toxin- and two-partner secretion systems among hyperinvasive and non-hyperinvasive lineages. By computationally screening also the core genome for signs of recombination, we provided evidence that about 40% of the meningococcal core genes are affected by recombination primarily within metabolic genes as well as genes involved in DNA replication and repair. By comparison with the results of previous mCGH studies, our data indicated that genetic structuring as revealed by mCGH is stable over time and highly similar for isolates from different geographic origins.
Recombination comprising lateral transfer of entire genes as well as homologous intragenic recombination has a profound impact on meningococcal population structure and genome composition. Our data support the hypothesis that meningococcal virulence is polygenic in nature and that differences in metabolism might contribute to virulence.