Acquisition of the capsule locus by horizontal gene transfer in Neisseria meningitidis is often accompanied by the loss of UDP-GalNAc synthesis

Abstract

Pathogenic meningococci have acquired a 24 kb capsule synthesis island (cps) by horizontal gene transfer which consists of a synthetic locus and associated capsule transport genes flanked by repetitive Regions D and D’. Regions D and D’ contain an intact gene encoding a UDP-galactose epimerase (galE1) and a truncated remnant (galE2), respectively. In this study, GalE protein alleles were shown to be either mono-functional, synthesising UDP-galactose (UDP-Gal), or bi-functional, synthesising UDP-Gal and UDP-galactosamine (UDP-GalNAc). Meningococci possessing a capsule null locus (cnl) typically possessed a single bi-functional galE. Separation of functionality between galE1 and galE2 alleles in meningococcal isolates was retained for all serogroups except serogroup E which has a synthetic requirement for UDP-GalNAc. The truncated galE2 remnant in Region D’ was also phylogenetically related to the bi-functional galE of the cnl locus suggesting common ancestry. A model is proposed in which the illegitimate recombination of the cps island into the galE allele of the cnl locus results in the formation of Region D’ containing the truncated galE2 locus and the capture of the cps island en bloc. The retention of the duplicated Regions D and D’ enables inversion of the synthetic locus within the cps island during bacterial growth.

Characterization of capsule genes in non-pathogenic Neisseria species

“…The latter is the most evolutionarily parsimonious explanation, although a scenario between these two extremes is also possible. Further support for an HGT event comes from the duplication of region D genes within the N. meningitidis cps , which is attributed to illegitimate recombination in the galE gene in a model proposed by Bartley et al [ 22 ]. A satisfactory alternative explanation for the organization of the meningococcal cps has not been proposed to date.…”

Virulence genes and previously unexplored gene clusters in four commensal Neisseria spp. isolated from the human throat expand the neisserial gene repertoire

“…The acquisition of the capsular genes by N. meningitidis from the non-pathogenic Neisseria spp. evolutionarily [7,101] and the recent discovery of meningococcal capsule genes in the newly described putatively named Neisseria brasiliensis [103] support the capacity for interspecies transfer of capsular genes between the non-pathogens and N. meningitidis. Although new meningococcal serogroups have not been identified in N. meningitidis, capsule switching could provide a means for circumventing the serogroup specific vaccines directed against it.…”

“…The structure of the capsule locus is well characterized and conserved in N. meningitidis [100,101] and phylogenetic analysis of Neisseria spp. capsule genes carried out by Clemence et al [7] highlighted that N. subflava was the closest encapsulated relative of N. meningitidis.…”

“…The capsule of some N. meningitidis serotypes are considered to be a major pathogenicity factor and its anti-phagocytic properties are essential for growth in the host's bloodstream [106]. Despite the defined role of the N. meningitidis capsule in virulence, its ecological role is not as well defined, as nonencapsulated N. meningitidis strains are able to grow and survive within the human nasopharynx as well as encapsulated strains, likely better [6,74,101]. Further research is needed to determine the role and nature of the potential capsules in the commensal isolates.…”

“…This analysis demonstrates additional reservoirs for antigenic variant alleles of NadA and Fhbp not represented in the vaccine that may allow N. meningitidis to escape vaccine-mediated control via HGT from commensal Neisseria spp. In concert with the potential role for commensal capsule loci to provide genetic material for capsule switching [6,101], the scope for evolution of this pathogen, and also for pharyngeal N. gonorrhoeae, through their natural competence preference for the neisserial DNA uptake sequence [78,81,82] likely contributes to genome plasticity [109].…”