Abstract
Background 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.Principal FindingsWe 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.ConclusionsRecombination 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.
Highlights
Neisseria meningitidis is a commensal exclusively of the human nasopharynx that is carried by about 20% of the human population [1,2]
Our data support the hypothesis that meningococcal virulence is polygenic in nature and that differences in metabolism might contribute to virulence
Analysis of meningococcal population structure by multilocus sequence typing (MLST) suggests that disease-causing meningococci belong to particular groups of related sequence types (STs), termed clonal complexes (CCs), that are overrepresented in disease isolates relative to their carriage prevalences, and that only few so called hyperinvasive lineages are responsible for most disease
Summary
Neisseria meningitidis is a commensal exclusively of the human nasopharynx that is carried by about 20% of the human population [1,2]. Analysis of meningococcal population structure by MLST suggests that disease-causing meningococci belong to particular groups of related sequence types (STs), termed clonal complexes (CCs), that are overrepresented in disease isolates relative to their carriage prevalences, and that only few so called hyperinvasive lineages are responsible for most disease [8]), one genomewide association study (GWAS) found an association between the MDA island belonging to the M13 family of filamentous prophages with disease-causing bacteria from hyperinvasive lineages [9]. This GWAS included only genes from a meningococcal serogroup A strain and missed all genes that are specific for the genetically variant serogroup B and C strains causing most disease in industrialized countries. 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
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