title: Regulation of capsule in Neisseria meningitidis.
abstract: Neisseria meningitidis, a devastating pathogen exclusive to humans, expresses capsular polysaccharides that are the major meningococcal virulence determinants and the basis for successful meningococcal vaccines. With rare exceptions, the expression of capsule (serogroups A, B, C, W, X, Y) is required for systemic invasive meningococcal disease. Changes in capsule expression or structure (e.g. hypo- or hyper-encapsulation, capsule "switching", acetylation) can influence immunologic diagnostic assays or lead to immune escape. The loss or down-regulation of capsule is also critical in meningococcal biology facilitating meningococcal attachment, microcolony formation and the carriage state at human mucosal surfaces. Encapsulated meningococci contain a cps locus with promoters located in an intergenic region between the biosynthesis and the conserved capsule transport operons. The cps intergenic region is transcriptionally regulated (and thus the amount of capsule expressed) by IS element insertion, by a two-component system, MisR/MisS and through sequence changes that result in post-transcriptional RNA thermoregulation. Reversible on-off phase variation of capsule expression is controlled by slipped strand mispairing of homo-polymeric tracts and by precise insertion and excision of IS elements (e.g. IS1301) in the biosynthesis operon. Capsule structure can be altered by phase-variable expression of capsular polymer modification enzymes or "switched" through transformation and homologous recombination of different polymerases. Understanding the complex regulation of meningococcal capsule has important implications for meningococcal biology, pathogenesis, diagnostics, current and future vaccine development and vaccine strategies.
authors.affiliation: a Department of Medicine , Emory University School of Medicine, Woodruff Health Sciences Center , Atlanta , GA , USA.
authors.forename: Yih-Ling
authors.initials: YL
authors.lastname: Tzeng
authors.affiliation: a Department of Medicine , Emory University School of Medicine, Woodruff Health Sciences Center , Atlanta , GA , USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Thomas
authors.affiliation: a Department of Medicine , Emory University School of Medicine, Woodruff Health Sciences Center , Atlanta , GA , USA.
authors.forename: David S
authors.initials: DS
authors.lastname: Stephens
mesh_terms: D000818:Animals; D016667:Bacterial Capsules / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D008589:Meningococcal Infections / Q000382:microbiology*; D009345:Neisseria meningitidis / Q000235:genetics* / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins
keywords: Bacterial virulence regulation; capsular polysaccharides; capsule switching; meningococcal diseases