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

Stephanie N Bartley,Timothy T Perkins,Alice Vrielink,Shakeel Mowlaboccus,Odile B Harrison,Martin C J Maiden,Charlene M Kahler,Christopher A Mullally,Keith A Stubbs

doi:10.1038/srep44442

Stephanie N Bartley, Timothy T Perkins + Show 7 more

Open Access

https://doi.org/10.1038/srep44442

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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.

Highlights

Pathogenic meningococci have acquired a 24 kb capsule synthesis island by horizontal gene transfer which consists of a synthetic locus and associated capsule transport genes flanked by repetitive Regions D and D’
Two meningococcal galE1 variants belonging to serogroup E and Z meningococci were found on the same branch as those from N. animalis and N. weaveri which were more distantly related to Cluster A and B
The acquisition of the cps island by horizontal gene transfer (HGT) into an ancestral non-pathogenic meningococcal lineage carrying a cnl locus similar to cc[53] and cc[198] isolates of N. meningitidis has been proposed by Schoen et al.[6] and others[21,22,23,24,25]. This hypothetical model proposes that the modern arrangement of the cps island is the outcome of at least two recombination events that resulted in the capture of Region A-C and Region B, located upstream and downstream of Region E, respectively, in the capsule null locus of non-pathogenic meningococci[8,9,10,26]

Summary

Introduction

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’. N. meningitidis is predominantly an opportunistic pathogen, asymptomatically colonising the mucosa of the nasopharynx of approximately 10% of the adult population[2,3] but occasionally invades the host, resulting in septicaemia and meningitis[4] In both N. meningitidis and N. gonorrhoeae, interactions with host cells are modulated by the glycome on the bacterial surface which includes the lipooligosaccharide (LOS) and the glycosylation status of the type IV pilin[5]. The general organisation of the cps island is as follows: Region A is responsible for the synthesis of the capsule polymer; Region B (ctrEF) and Region C (ctrABCD) contain genes responsible for transporting the capsule polymer to the bacterial surface while Region D and Region D’ contain an intact and truncated remnant copy of a gene encoding UDP-galactose epimerase, known as galE1 and galE2, respectively. The ancestral events leading to the formation of the cps island are unclear, serogroup switching can result in the replacement of the entire synthetic Region A in instances where serogroups B or C switch to serogroups A, W or Y (Fig. 1) indicating recombination events in this region continue to occur[11,12]

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