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PMID: 10722605 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Molecular and biological analysis of eight genetic islands that distinguish Neisseria meningitidis from the closely related pathogen Neisseria gonorrhoeae.

Infection and immunity ·Vol. 68 ·No. 4 ·2000-04-00 ·Pages 2082-95

Klee SR, Nassif X, Kusecek B, Merker P, Beretti JL, Achtman M, Tinsley CR

Abstract

The pathogenic species Neisseria meningitidis and Neisseria gonorrhoeae cause dramatically different diseases despite strong relatedness at the genetic and biochemical levels. N. meningitidis can cross the blood-brain barrier to cause meningitis and has a propensity for toxic septicemia unlike N. gonorrhoeae. We previously used subtractive hybridization to identify DNA sequences which might encode functions specific to bacteremia and invasion of the meninges because they are specific to N. meningitidis and absent from N. gonorrhoeae. In this report we show that these sequences mark eight genetic islands that range in size from 1.8 to 40 kb and whose chromosomal location is constant. Five of these genetic islands were conserved within a representative set of strains and/or carried genes with homologies to known virulence factors in other species. These were deleted, and the mutants were tested for correlates of virulence in vitro and in vivo. This strategy identified one island, region 8, which is needed to induce bacteremia in an infant rat model of meningococcal infection. Region 8 encodes a putative siderophore receptor and a disulfide oxidoreductase. None of the deleted mutants was modified in its resistance to the bactericidal effect of serum. Neither were the mutant strains altered in their ability to interact with endothelial cells, suggesting that such interactions are not encoded by large genetic islands in N. meningitidis.

MeSH Terms
Animals Bacteremia/microbiology Bacterial Adhesion Blotting, Southern Complement System Proteins/genetics Conserved Sequence DNA, Bacterial Gene Deletion Gene Library Gonorrhea/microbiology Meningococcal Infections/microbiology Models, Genetic Molecular Sequence Data Mutagenesis, Insertional Neisseria gonorrhoeae/genetics,pathogenicity Neisseria meningitidis/genetics,pathogenicity Nucleic Acid Hybridization Open Reading Frames Polymerase Chain Reaction Rabbits Rats Rats, Inbred Lew Sequence Analysis, DNA Species Specificity Transformation, Bacterial Virulence
Chemicals
DNA, Bacterial Complement System Proteins
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Klee S R
Max-Planck Institut für Molekulare Genetik, 14195 Berlin, Germany.
Nassif X
Kusecek B
Merker P
Beretti J L
Achtman M
Tinsley C R
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Article Info
Journal
Infection and immunity
Abbr.
Infect Immun
ISSN
0019-9567
DOI
10.1128/IAI.68.4.2082-2095.2000
Published
2000-04-00
Pages
2082-95
Language
English
Region
United States
NLM ID
0246127
PMCID
PMC97389
Subset
IM
Databases
GENBANK
AJ391255, AJ391256, AJ391257, AJ391258, AJ391259, AJ391260, AJ391261, AJ391262, AJ391263, AJ391264, AJ391265, AJ391266, AJ391267, AJ391268, AJ391269, AJ391270, AJ391271, AJ391272, AJ391273, AJ391274, AJ391275, AJ391276, AJ391277, AJ391278, AJ391279, AJ391280, AJ391281, AJ391282, AJ391283, AJ391284
External Links
PubMed source DOI: 10.1128/IAI.68.4.2082-2095.2000 PMC Full Text View journal details
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