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2016 ; 42
(5
): 759-72
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Regulation of capsule in Neisseria meningitidis
#MMPMID26089023
Tzeng YL
; Thomas J
; Stephens DS
Crit Rev Microbiol
2016[Sep]; 42
(5
): 759-72
PMID26089023
show ga
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.
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