Neisseria meningitidis has acquired sequences within the capsule locus by horizontal genetic transfer

Abstract

Background:Expression of a capsule from one of serogroups A, B, C, W, X or Y is usually required forNeisseria meningitidis(Nme) to cause invasive meningococcal disease. The capsule is encoded by the capsule locus,cps, which is proposed to have been acquired by a formerly capsule null organism by horizontal genetic transfer (HGT) from another species. Following identification of putative capsule genes in non-pathogenicNeisseriaspecies, this hypothesis is re-examined.Methods:Whole genome sequence data fromNeisseriaspecies, includingNmegenomes from a diverse range of clonal complexes and capsule genogroups, and non-Neisseriaspecies, were obtained from PubMLST and GenBank. Sequence alignments of genes from the meningococcalcps, and predicted orthologues in other species, were analysed using Neighbor-nets, BOOTSCANing and maximum likelihood phylogenies.Results:The meningococcalcpswas highly mosaic within regions B, C and D. A subset of sequences within regions B and C were phylogenetically nested within homologous sequences belonging toN. subflava, consistent with HGT event in whichN. subflavawas the donor. In thecpsof 23/39 isolates, the two copies of region D were highly divergent, withrfbABC’sequences being more closely related to predicted orthologues in the proposed speciesN. weixii (GenBank accession numberCP023429.1) than the same genes inNmeisolates lacking a capsule. There was also evidence of mosaicism in therfbABC’sequences of the remaining 16 isolates, as well asrfbABCfrom many isolates.Conclusions:Data are consistent with theen blocacquisition ofcpsin meningococci fromN. subflava, followed by further recombination events with otherNeisseriaspecies. Nevertheless, the data cannot refute an alternative model, in which native meningococcal capsule existed prior to undergoing HGT withN. subflavaand other species. Within-genus recombination events may have given rise to the diversity of meningococcal capsule serogroups.