Acquisition of the capsule locus in <em>Neisseria meningitidis </em>and the loss of N-acetylgalactosamine biosynthesis  — ASN Events
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Acquisition of the capsule locus in Neisseria meningitidis and the loss of N-acetylgalactosamine biosynthesis  (#93)

Stephanie N Bartley 1 , Keith Stubbs 1 , Alice Vrielink 1 , Shakeel Mowlaboccus 1 , Christopher Mullally 1 , Martin C.J Maiden 2 , Odile B Harrison 2 , Timothy Perkins 1 , Charlene M Kahler 1
  1. School of Biomedical Sciences, University Of Western Australia, CRAWLEY, WA, Australia
  2. Oxford University, Oxford, United Kingdom

The acquisition of virulence determinants by horizontal gene transfer (HGT) contributes to the evolution of pathogens from commensal bacterial species. Neisseria meningitidis resides in the nasopharynx of humans and causes epidemic meningitis. Typically pathogenic isolates express a capsule which is essential for invasive disease whilst non-disease isolates typically do not express a capsule. The 25 kb capsule synthesis island (cps) has been acquired by HGT and consists of a synthetic locus (region A) and associated capsule transport genes (region C) flanked by a repetitive region D and D’. Region E containing a gene of unknown function and Region B encoding capsule transport accessory proteins, CtrE and CtrF, complete the locus. Region D’ and region D contain a truncated and intact UDP-galactose epimerase, GalE, respectively. GalE is necessary for the synthesis of UDP-galactose (UDP-Gal) which is utilised in the synthesis of lipopolysaccharide. Functional archaeology of the GalE allele has revealed that there are two functional categories: a mono-functional enzyme which can only synthesise UDP-Gal, and a second bi-functional enzyme with the capacity to also synthesise UDP-galactosamine (UDP-GalNAc). Non-disease causing meningococci possessing a capsule null locus (cnl) with region E and D only, usually contain a single bi-functional GalE allele. Conversely, region D of most encapsulated meningococci contains a mono-functional galE1 that has lost the capacity to synthesize UDP-GalNAc. Region D’ is characterised by a truncated bi-functional galE2 allele. A carriage meningococcal isolate with an unusual arrangement of Region B-D only carries an intact mono-functional galE allele. These observations suggest that the meningococcal cps island is the result of two HGT events. One HGT event is the acquisition of Region B (ctrEF) downstream of region D containing a bi-functional galE in a cnl meningococcus. A second HGT cassette containing region A-C-E-D’ usually carrying a truncated bi-functional GalE allele is then acquired to create the final structure.

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