Dataset Information

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.

SUBMITTER: Bartley SN

PROVIDER: S-EPMC5349592 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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

Bartley Stephanie N SN Mowlaboccus Shakeel S Mullally Christopher A CA Stubbs Keith A KA Vrielink Alice A Maiden Martin C J MC Harrison Odile B OB Perkins Timothy T TT Kahler Charlene M CM

Scientific reports 20170314

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- ...[more]

PMID: 28290510

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Project description:Background: Expression of a capsule from one of serogroups A, B, C, W, X or Y is usually required for Neisseria 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-pathogenic Neisseria species, this hypothesis is re-examined. Methods: Whole genome sequence data from Neisseria species, including Nme genomes from a diverse range of clonal complexes and capsule genogroups, and non- Neisseria species, were obtained from PubMLST and GenBank. Sequence alignments of genes from the meningococcal cps, and predicted orthologues in other species, were analysed using Neighbor-nets, BOOTSCANing and maximum likelihood phylogenies. Results: The meningococcal cps was highly mosaic within regions B, C and D. A subset of sequences within regions B and C were phylogenetically nested within homologous sequences belonging to N. subflava, consistent with HGT event in which N. subflava was the donor. In the cps of 23/39 isolates, the two copies of region D were highly divergent, with rfbABC' sequences being more closely related to predicted orthologues in the proposed species N. weixii (GenBank accession number CP023429.1) than the same genes in Nme isolates lacking a capsule. There was also evidence of mosaicism in the rfbABC' sequences of the remaining 16 isolates, as well as rfbABC from many isolates. Conclusions: Data are consistent with the en bloc acquisition of cps in meningococci from N. subflava, followed by further recombination events with other Neisseria species. Nevertheless, the data cannot refute an alternative model, in which native meningococcal capsule existed prior to undergoing HGT with N. subflava and other species. Within-genus recombination events may have given rise to the diversity of meningococcal capsule serogroups.

Project description:Neisseria meningitidis is the etiologic agent of epidemic bacterial meningitis. Lipooligosaccharide (LOS) is a principal virulence factor associated with the organism, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of LOS has demonstrated that there is considerable microheterogeneity in the molecule. To begin our understanding of the nature of this heterogeneity, we identified a Tn916-generated LOS mutant of N. meningitidis NMB (serotype L3, monoclonal antibodies 3F11+, 6B4+, and 4C4-) that was designated NMB-SS3 (monoclonal antibodies 3F11-, 6B4-, and 4C4+). The transposon insertion was localized to the amino terminus of the functional copy of the UDP-Glc 4-epimerase gene (galE). UDP-Glc 4-epimerase (EC 5.1.3.2) activity was present in N. meningitidis NMB but not in NMB-SS3, indicating that the Tn916 insertion had abolished this activity. Mass spectrometric analysis of the LOS from strain NMB revealed multiple species of LOS, which is consistent with extensive microheterogeneity. While the most predominant structure was consistent with a terminal lacto-N-neotetrose structure found in other strains of N. meningitidis, Gal beta 1-->4GlcNAc beta 1-->3Gal beta 1-->4Glc-->(GlcNAc)-->Hep2PEA-->KDO2 (where Hep is heptose, PEA is phosphoethanolamine, and KDO is 2-keto-3-deoxymannooctulosonic acid), structures containing repetitive hexoses which are not precursors of this structure were also identified. Compositional analysis of LOS from strain NMB-SS3 revealed that there were no galactoses present in the structure. Mass spectrometric analysis of O-deacylated LOS revealed the presence of multiple species, with the predominant LOS species in this mutant strain formed by the Hex-->(HexNAc)-->Hep2PEA-->KDO2 (where Hex is hexose and HexNAc is N-acetylhexosamine) structure. However, LOS structures with repetitive hexoses, e.g., Hexn-->(HexNAc)-->Hep2PEA-->KDO2 (n = 2, 3, or 4), emanating from one or both heptoses were also identified. Since this mutant cannot synthesize UDP-Gal, these structures must repetitive glucoses. These data suggest that NMB has a glycosyltransferase capable of polymerizing glucose moieties as an alternative biosynthetic pathway to the wild-type lacto-N-neotetrose structure.

Dataset Information

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

Publications

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

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