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PMID: 8598202 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Modulation of cell surface sialic acid expression in Neisseria meningitidis via a transposable genetic element.

The EMBO journal ·Vol. 15 ·No. 1 ·1996-01-02 ·Pages 192-8

Hammerschmidt S, Hilse R, van Putten JP, Gerardy-Schahn R, Unkmeir A, Frosch M

Abstract

Cell surface-located sialic acids of the capsule and the lipooligosaccharide (LOS) are both pivotal virulence factors in Neisseria meningitidis, promoting survival and dissemination of this pathogen which can cause both sepsis and meningitis. With the aid of a unique set of isogenic meningococcal mutants defective in the expression of cell surface-located sialic acids, we have demonstrated that encapsulation hinders the primary event in the development of the disease, but the spontaneous switching of encapsulated wild-type bacteria to a capsule-negative phenotype promotes meningococcal adherence and invasion into mucosal epithelial cells. Genetic analysis of the capsule-negative, invasive bacteria revealed a unique mechanism for modulation of capsule expression based on the reversible inactivation of an essential sialic acid biosynthesis gene, siaA, by insertion/excision of a naturally occurring insertion sequence element, IS1301. Inactivation of siaA regulates both capsule expression and endogenous LOS sialylation. This is the first example of an insertion sequence element-based genetic switch mechanism in the pathogenic bacterium and is an important step in the understanding of bacterial virulence.

MeSH Terms
Amino Acid Sequence Antigenic Variation Bacterial Adhesion Bacterial Capsules/metabolism Base Sequence Cells, Cultured DNA Transposable Elements DNA, Bacterial/chemistry Gene Expression Regulation, Bacterial Humans Lipopolysaccharides/metabolism Molecular Sequence Data N-Acetylneuraminic Acid Neisseria meningitidis/cytology,metabolism,pathogenicity Sialic Acids/metabolism
Chemicals
DNA Transposable Elements DNA, Bacterial Lipopolysaccharides Sialic Acids lipid-linked oligosaccharides N-Acetylneuraminic Acid
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Hammerschmidt S
Institut fur Medizinische Mikrobiologie, Medizinische Hoschschule Hannover, Germany.
Hilse R
van Putten J P
Gerardy-Schahn R
Unkmeir A
Frosch M
References (27)
27 references, click to expand
  1. Preferential transposition of an IS630-associated composite transposon to TA in the 5'-CTAG-3' sequence.
    J Bacteriol. 1991 Oct;173(19):6207-12 PMID: 1655702
  2. Transposition in Shigella dysenteriae: isolation and analysis of IS911, a new member of the IS3 group of insertion sequences.
    J Bacteriol. 1990 Jul;172(7):4090-9 PMID: 2163395
  3. Strucutres of the capsular polysaccharides of Neisseria meningitidis as determined by 13C-nuclear magnetic resonance spectroscopy.
    J Infect Dis. 1977 Aug;136 Suppl:S78-83 PMID: 408435
  4. Meningococcal Opa and Opc proteins: their role in colonization and invasion of human epithelial and endothelial cells.
    Mol Microbiol. 1993 Nov;10(3):499-510 PMID: 7968528
  5. Genetic variation in pathogenic bacteria.
    Trends Genet. 1992 Dec;8(12):422-7 PMID: 1362826
  6. A retrovirus-like strategy for expression of a fusion protein encoded by yeast transposon Ty1.
    Nature. 1985 Jan 17-23;313(5999):243-6 PMID: 2982101
  7. Molecular analysis of the biosynthesis pathway of the alpha-2,8 polysialic acid capsule by Neisseria meningitidis serogroup B.
    Mol Microbiol. 1994 Oct;14(1):141-9 PMID: 7830552
  8. In vitro and in vivo modification of Neisseria gonorrhoeae lipooligosaccharide epitope structure by sialylation.
    J Exp Med. 1990 May 1;171(5):1649-64 PMID: 1692081
  9. Specific insertion and deletion of insertion sequence 1-like DNA element causes the reversible expression of the virulence capsular antigen Vi of Citrobacter freundii in Escherichia coli.
    Proc Natl Acad Sci U S A. 1988 Jun;85(12):4402-5 PMID: 2837765
  10. Evidence for a common molecular origin of the capsule gene loci in gram-negative bacteria expressing group II capsular polysaccharides.
    Mol Microbiol. 1991 May;5(5):1251-63 PMID: 1659649
  11. Molecular characterization and expression in Escherichia coli of the gene complex encoding the polysaccharide capsule of Neisseria meningitidis group B.
    Proc Natl Acad Sci U S A. 1989 Mar;86(5):1669-73 PMID: 2493648
  12. Variable expression of extracellular polysaccharide in the marine bacterium Pseudomonas atlantica is controlled by genome rearrangement.
    Proc Natl Acad Sci U S A. 1988 Jun;85(11):3923-7 PMID: 16593937
  13. Neisseria meningitidis infection in mice: influence of iron, variations in virulence among strains, and pathology.
    Infect Immun. 1979 May;24(2):545-51 PMID: 110703
  14. Expression of the Opc protein correlates with invasion of epithelial and endothelial cells by Neisseria meningitidis.
    Mol Microbiol. 1992 Oct;6(19):2785-95 PMID: 1435257
  15. NZB mouse system for production of monoclonal antibodies to weak bacterial antigens: isolation of an IgG antibody to the polysaccharide capsules of Escherichia coli K1 and group B meningococci.
    Proc Natl Acad Sci U S A. 1985 Feb;82(4):1194-8 PMID: 3919387
  16. Detection of Mycoplasma pneumoniae by polymerase chain reaction and nonradioactive hybridization in microtiter plates.
    J Clin Microbiol. 1993 May;31(5):1088-94 PMID: 8501208
  17. Generation of capsule-deficient Neisseria meningitidis strains by homologous recombination.
    Mol Microbiol. 1990 Jul;4(7):1215-8 PMID: 2122175
  18. Effect of the (alpha 2-->8)-linked polysialic acid capsule on adherence of Neisseria meningitidis to human mucosal cells.
    J Infect Dis. 1993 Feb;167(2):475-9 PMID: 8380612
  19. Pathogenic events during infection of the human nasopharynx with Neisseria meningitidis and Haemophilus influenzae.
    Rev Infect Dis. 1991 Jan-Feb;13(1):22-33 PMID: 1901998
  20. Sequence and characterization of an insertion sequence, IS711, from Brucella ovis.
    Gene. 1993 Oct 29;133(1):123-7 PMID: 8224885
  21. Detection and some properties of the sialyltransferase implicated in the sialylation of lipopolysaccharide of Neisseria gonorrhoeae.
    Microb Pathog. 1993 Apr;14(4):307-13 PMID: 8326854
  22. Bacterial meningitis in the United States, 1978 through 1981. The National Bacterial Meningitis Surveillance Study.
    JAMA. 1985 Mar 22-29;253(12):1749-54 PMID: 3871869
  23. Frameshifting is required for production of the transposase encoded by insertion sequence 1.
    Proc Natl Acad Sci U S A. 1989 Jun;86(12):4609-13 PMID: 2543983
  24. Contribution of genes from the capsule gene complex (cps) to lipooligosaccharide biosynthesis and serum resistance in Neisseria meningitidis.
    Mol Microbiol. 1994 Mar;11(5):885-96 PMID: 8022265
  25. Epidemiology of meningococcal infections in the Federal Republic of Germany, 1966-1984.
    Zentralbl Bakteriol Mikrobiol Hyg A. 1988 Mar;268(1):83-102 PMID: 3394448
  26. Recognition and control of neisserial infection by antibody and complement.
    Trends Microbiol. 1995 May;3(5):198-201 PMID: 7627458
  27. Phase variation of lipopolysaccharide directs interconversion of invasive and immuno-resistant phenotypes of Neisseria gonorrhoeae.
    EMBO J. 1993 Nov;12(11):4043-51 PMID: 7693451
Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1996-01-02
Pages
192-8
Language
English
Region
England
NLM ID
8208664
PMCID
PMC449931
Subset
IM
Databases
GENBANK
Z49092
External Links
PubMed source PMC Full Text View journal details
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