Whole-genome comparison of disease and carriage strains provides insights into virulence evolution in Neisseria meningitidis

Abstract

Neisseria meningitidis is a leading cause of infectious childhood mortality worldwide. Most research efforts have hitherto focused on disease isolates belonging to only a few hypervirulent clonal lineages. However, up to 10% of the healthy human population is temporarily colonized by genetically diverse strains mostly with little or no pathogenic potential. Currently, little is known about the biology of carriage strains and their evolutionary relationship with disease isolates. The expression of a polysaccharide capsule is the only trait that has been convincingly linked to the pathogenic potential of N. meningitidis. To gain insight into the evolution of virulence traits in this species, whole-genome sequences of three meningococcal carriage isolates were obtained. Gene content comparisons with the available genome sequences from three disease isolates indicate that there is no core pathogenome in N. meningitidis. A comparison of the chromosome structure suggests that a filamentous prophage has mediated large chromosomal rearrangements and the translocation of some candidate virulence genes. Interspecific comparison of the available Neisseria genome sequences and dot blot hybridizations further indicate that the insertion sequence IS1655 is restricted only to N. meningitidis; its low sequence diversity is an indicator of an evolutionarily recent population bottleneck. A genome-based phylogenetic reconstruction provides evidence that N. meningitidis has emerged as an unencapsulated human commensal from a common ancestor with Neisseria gonorrhoeae and Neisseria lactamica and consecutively acquired the genes responsible for capsule synthesis via horizontal gene transfer.comparative genomics ͉ genome evolution ͉ bacterial capsule ͉ neisserial prophage ͉ IS1655

Whole-Genome Sequence of the Transformable Neisseria meningitidis Serogroup A Strain WUE2594

“…It contains four rRNA operons and codes for 55 tRNAs, 1,941 protein-coding sequences (CDSs), and 135 pseudogenes. In line with a clonal population structure of serogroup A meningococci (1), the WUE2594 genome has the highest similarity to the genome of Z2491 among the seven so far completely sequenced meningococcal strains (2,7,11,12,15,16,19). Both share 1,857 CDSs, with an average nucleotide sequence identity of 98.6%, and are highly colinear, with only one inversion spanning the capsule locus regions A, C, and E (5).…”

Lateral genetic transfer: open issues

“…A comparative analysis of 12 strains of Prochlorococcus marinus revealed conserved core genes, sets of genes that are ubiquitous in and exclusive to high-lightand low-light-adapted subsets of the group, plus accessory genes specific to one or a few strains (Kettler et al 2007); strain-restricted functions include viral defence and transport of toxins. Association of adaptive genes by ecotype or lifestyle is compelling, but candidate virulence genes in Neisseria (Schoen et al 2008) and Streptococcus (McMillan et al 2006) do not preferentially associate with virulent strains, suggesting that sequence variation can be important. Eppinger et al (2004) identified a 'flexible gene pool' for four Campylobacter species comprising plasmids, phage elements, mobile DNA and genomic islets and DNA-restriction/modification systems.…”

Genome Sequence of a Neisseria meningitidis Capsule Null Locus Strain from the Clonal Complex of Sequence Type 198

“…Whereas CC ST-53 cnl strains can be found frequently in carriers but almost never in cases of IMD, ST-198 cnl strains were found in two of four reported IMD cases caused by cnl strains (6, 7). Here we provide the genome sequence of an N. meningitidis cnl strain of CC and compare it to the genome of cnl strain ␣14 of CC ST-53 (12).…”

“…We used the Roche GS De Novo Assembler software for the assembly of the Roche/454 sequence data and the CONSED (5) software package for guidance during the finishing phase and obtained a draft genome consisting of two scaffolds and 41 scaffolded contigs. The N. meningitidis ␣704 scaffolds and 11 unscaffolded contigs were arranged according to the N. meningitidis ␣14 reference genome (12) and concatenated by 12-mer linkers (CTA GCTAGCTAG). Annotation of the N. meningitidis ␣704 genome was performed with GenDB (9) using the NeMeSys annotation of ␣14 as a reference (10).…”