Dataset Information

Antigenic variation of the class I outer membrane protein in hyperendemic Neisseria meningitidis strains in the netherlands.

ABSTRACT: Since 1980, the number of cases of meningococcal disease caused by serogroup B isolates with the P1.4 serosubtype has greatly increased in The Netherlands. Screening for this serosubtype in the strain collection of The Netherlands Reference Laboratory for Bacterial Meningitis revealed that a low number of P1.4 strains had been present in the Dutch meningococcal population since 1965. Genotyping of P1.4 strains showed that one cluster of strains, the hyperendemic lineage III (D. A. Caugant et al., J. Infect. Dis. 162:867-874, 1990), is responsible for the increase since 1980. The diversity of the porA genes, which encode the P1 protein on which serosubtyping is based, was studied for genotypically different P1.4 strains and for lineage III strains expressing antigenically different P1 proteins. Sequence analysis showed that porA genes of genotypically distinct strains that express antigenically indistinguishable P1 proteins are identical only in the epitope-encoding region, suggesting that this region has spread through the meningococcal population via horizontal gene transfer. Analysis of porA genes of lineage III strains showed that both horizontal gene transfer and partial deletion of the epitope-encoding region may contribute to the different antigenic properties for P1 of these strains. Phase variation of expression of the porA gene seems to account for most nonreacting strains. These results show that serosubtyping may underestimate the rise of a hyperendemic clone.

SUBMITTER: Bart A

PROVIDER: S-EPMC96663 | biostudies-literature | 1999 Aug

REPOSITORIES: biostudies-literature

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Antigenic variation of the class I outer membrane protein in hyperendemic Neisseria meningitidis strains in the netherlands.

Bart A A Dankert J J van der Ende A A

Infection and immunity 19990801 8

Since 1980, the number of cases of meningococcal disease caused by serogroup B isolates with the P1.4 serosubtype has greatly increased in The Netherlands. Screening for this serosubtype in the strain collection of The Netherlands Reference Laboratory for Bacterial Meningitis revealed that a low number of P1.4 strains had been present in the Dutch meningococcal population since 1965. Genotyping of P1.4 strains showed that one cluster of strains, the hyperendemic lineage III (D. A. Caugant et al. ...[more]

PMID: 10417147

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Project description:BackgroundOuter membrane vesicles (OMVs) are nanoparticles released by Gram-negative bacteria and can be used as vaccines. Often, detergents are used to promote release of OMVs and to remove the toxic lipopolysaccharides. Lipopolysaccharides can be detoxified by genetic modification such that vesicles spontaneously produced by bacteria can be directly used as vaccines. The use of spontaneous OMVs has the advantage that no separate extraction step is required in the purification process. However, the productivity of spontaneous OMVs by bacteria at optimal growth conditions is low. One of many methods for increasing OMV formation is to reduce the linkage of the outer membrane to the peptidoglycan layer by knocking out the rmpM gene. A previous study showed that for Neisseria meningitidis this resulted in release of more OMVs. Furthermore, cysteine depletion was found to trigger OMV release and at the same time cause reduced growth and oxidative stress responses. Here we study the effect of growth rate and oxidative stress on OMV release.ResultsFirst, we identified using chemostat and accelerostat cultures of N. meningitidis that increasing the growth rate from 0.03 to 0.18 h-1 has a limited effect on OMV productivity. Thus, we hypothesized that oxidative stress is the trigger for OMV release and that oxidative stress can be introduced directly by increasing the dissolved oxygen tension of bacterial cultures. Slowly increasing oxygen concentrations in a N. meningitidis changestat showed that an increase from 30 to 150% air saturation improved OMV productivity four-fold. Batch cultures controlled at 100% air saturation increased OMV productivity three-fold over batch cultures controlled at 30% air saturation.ConclusionIncreased dissolved oxygen tension induces the release of outer membrane vesicles in N. meningitidis cultures. Since oxygen concentration is a well-controlled process parameter of bacterial cultures, this trigger can be applied as a convenient process parameter to induce OMV release in bacterial cultures. Improved productivity of OMVs not only improves the production costs of OMVs as vaccines, it also facilitates the use of OMVs as adjuvants, enzyme carriers, or cell-specific drug delivery vehicles.

Dataset Information

Antigenic variation of the class I outer membrane protein in hyperendemic Neisseria meningitidis strains in the netherlands.

Publications

Antigenic variation of the class I outer membrane protein in hyperendemic Neisseria meningitidis strains in the netherlands.

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